Enzyme inhibitor - Knowledge

3172: 771:. These three types of inhibition result respectively from the inhibitor binding only to the enzyme E in the absence of substrate S, to the enzyme–substrate complex ES, or to both. The division of these classes arises from a problem in their derivation and results in the need to use two different binding constants for one binding event. It is further assumed that binding of the inhibitor to the enzyme results in 100% inhibition and fails to consider the possibility of partial inhibition. The common form of the inhibitory term also obscures the relationship between the inhibitor binding to the enzyme and its relationship to any other binding term be it the Michaelis–Menten equation or a dose response curve associated with ligand receptor binding. To demonstrate the relationship the following rearrangement can be made: 3255: 368: 1462: 33: 380: 2182: 2799: 3000: 777: 3720: 2981: 2785: 2817: 3548: 3292: 1457:{\displaystyle {\begin{aligned}{\cfrac {V_{\max }}{1+{\cfrac {\ce {}}{K_{i}}}}}&={V_{\max }}\left({\cfrac {K_{i}}{K_{i}+}}\right)&&{\text{multiply by }}{\cfrac {K_{i}}{K_{i}}}=1\\&={V_{\max }}\left({\cfrac {K_{i}+-}{K_{i}+}}\right)&&{\text{add }}-=0{\text{ to numerator}}\\&={V_{\max }}\left(1-{\cfrac {}{K_{i}+}}\right)&&{\text{simplify }}{\cfrac {K_{i}+}{K_{i}+}}=1\\&=V_{\max }-V_{\max }{\cfrac {\ce {}}{K_{i}+}}&&{\text{multiply out by }}V_{\max }\end{aligned}}} 3861: 3728: 4202: 274:, which are not essential to the organism that produces them, but provide the organism with an evolutionary advantage, in that they can be used to repel predators or competing organisms or immobilize prey. In addition, many drugs are small molecule enzyme inhibitors that target either disease-modifying enzymes in the patient or enzymes in pathogens which are required for the growth and reproduction of the pathogen. 2957:

where the kinases interact with their substrate proteins, and most proteins are present inside cells at concentrations much lower than the concentration of ATP. As a consequence, if two protein kinase inhibitors both bind in the active site with similar affinity, but only one has to compete with ATP, then the competitive inhibitor at the protein-binding site will inhibit the enzyme more effectively.

2618:, respectively. However, the modified Michaelis-Menten equation assumes that binding of the inhibitor to the enzyme has reached equilibrium, which may be a very slow process for inhibitors with sub-nanomolar dissociation constants. In these cases the inhibition becomes effectively irreversible, hence it is more practical to treat such tight-binding inhibitors as irreversible (see 4112: 337:("regular" orientation) inhibitors. The mechanism of orthosteric inhibition is simply to prevent substrate binding to the enzyme through direct competition which in turn prevents the enzyme from catalysing the conversion of substrates into products. Alternatively, the inhibitor can bind to a site remote from the enzyme active site. These are known as 3267:

of these inhibitors rapidly bind to the enzyme in a low-affinity EI complex and this then undergoes a slower rearrangement to a very tightly bound EI* complex (see the "irreversible inhibition mechanism" diagram). This kinetic behaviour is called slow-binding. This slow rearrangement after binding often involves a

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Figure 1C: Clinical success of privileged protein family classes (% approved drugs targeting each target class): Reductase 7.62, Kinase 5.94, Protease 3.35, Hydrolase 2.76, NPTase 2.09, Transferase 1.92, Lyase 1.59, Isomerase 1.51, Phosphodiesterase 1.50, Cytochrome p450 0.84, Epigenetic eraser 0.33,

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Substrate or product inhibition is where either an enzymes substrate or product also act as an inhibitor. This inhibition may follow the competitive, uncompetitive or mixed patterns. In substrate inhibition there is a progressive decrease in activity at high substrate concentrations, potentially from

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protein in the pancreas. This inhibitor binds tightly to trypsin, preventing the trypsin activity that would otherwise be detrimental to the organ. Although the trypsin inhibitor is a protein, it avoids being hydrolysed as a substrate by the protease by excluding water from trypsin's active site and

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Not all irreversible inhibitors form covalent adducts with their enzyme targets. Some reversible inhibitors bind so tightly to their target enzyme that they are essentially irreversible. These tight-binding inhibitors may show kinetics similar to covalent irreversible inhibitors. In these cases some

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Irreversible inhibitors first form a reversible non-covalent complex with the enzyme (EI or ESI). Subsequently, a chemical reaction occurs between the enzyme and inhibitor to produce the covalently modified "dead-end complex" EI* (an irreversible covalent complex). The rate at which EI* is formed is

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The mechanism of partially competitive inhibition is similar to that of non-competitive, except that the EIS complex has catalytic activity, which may be lower or even higher (partially competitive activation) than that of the enzyme–substrate (ES) complex. This inhibition typically displays a lower

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These four types of inhibition can also be distinguished by the effect of increasing the substrate concentration on the degree of inhibition caused by a given amount of inhibitor. For competitive inhibition the degree of inhibition is reduced by increasing , for noncompetitive inhibition the degree

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concentrations of substrate , this type of inhibition can be reduced (due to the competitive contribution), but not entirely overcome (due to the noncompetitive component). Although it is possible for mixed-type inhibitors to bind in the active site, this type of inhibition generally results from an

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but does not affect the binding of substrate. This type of inhibitor binds with equal affinity to the free enzyme as to the enzyme-substrate complex. It can be thought of as having the ability of competitive and uncompetitive inhibitors, but with no preference to either type. As a result, the extent

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the effect of the inhibitor is a result of the percent of the enzyme population interacting with inhibitor. The only problem with this equation in its present form is that it assumes absolute inhibition of the enzyme with inhibitor binding, when in fact there can be a wide range of effects anywhere

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When an enzyme has multiple substrates, inhibitors can show different types of inhibition depending on which substrate is considered. This results from the active site containing two different binding sites within the active site, one for each substrate. For example, an inhibitor might compete with

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and are so diverse that there are probably natural inhibitors for most metabolic processes. The metabolic processes targeted by natural poisons encompass more than enzymes in metabolic pathways and can also include the inhibition of receptor, channel and structural protein functions in a cell. For

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inhibitors have chemical structures that are similar to ATP, one of the substrates of these enzymes. However, drugs that are simple competitive inhibitors will have to compete with the high concentrations of ATP in the cell. Protein kinases can also be inhibited by competition at the binding sites

2199:, the concentration at which the inhibitor half occupies the enzyme. In non-competitive inhibition the inhibitor can also bind to the enzyme-substrate complex, and the presence of bound substrate can change the affinity of the inhibitor for the enzyme, resulting in a second dissociation constant 3926:

is facilitated when an enzyme that is essential to the pathogen's survival is absent or very different in humans. Humans do not make peptidoglycan, therefore antibiotics that inhibit this process are selectively toxic to bacteria. Selective toxicity is also produced in antibiotics by exploiting

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In some cases, the inhibitor may bind to a distinct site on the enzyme that is in allosteric communication with the substrate binding pocket. In many cases, allosteric, substrate competitive compounds result in conformational changes to the enzyme that change the ability of the enzyme to bind

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the inhibitor may bind to the enzyme whether or not the substrate has already bound. Hence mixed inhibition is a combination of competitive and noncompetitive inhibition. Furthermore, the affinity of the inhibitor for the free enzyme and the enzyme-substrate complex may differ. By increasing

3192:. Since formation of EI may compete with ES, binding of irreversible inhibitors can be prevented by competition either with substrate or with a second, reversible inhibitor. This protection effect is good evidence of a specific reaction of the irreversible inhibitor with the active site. 2455: 620:

scheme (shown in the "inhibition mechanism schematic" diagram), an enzyme (E) binds to its substrate (S) to form the enzyme–substrate complex ES. Upon catalysis, this complex breaks down to release product P and free enzyme. The inhibitor (I) can bind to either E or ES with the

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inhibit the enzymes that produce and then cross-link the strands of this polymer together. This causes the cell wall to lose strength and the bacteria to burst. In the figure, a molecule of penicillin (shown in a ball-and-stick form) is shown bound to its target, the

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Competitive inhibitors usually bind to the active site. Non-competitive bind to a remote (allosteric) site. Uncompetitive inhibitors only bind once the substrate is bound, fully disrupting catalysis, and mixed inhibition is similar but with only partial disruption of

2739:(a change in shape) to a second more tightly held complex, EI*, but the overall inhibition process is reversible. This manifests itself as slowly increasing enzyme inhibition. Under these conditions, traditional Michaelis–Menten kinetics give a false value for 1875:

This term can then define the residual enzymatic activity present when the inhibitor is interacting with individual enzymes in the population. However the inclusion of this term has the added value of allowing for the possibility of activation if the secondary

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As enzymes have evolved to bind their substrates tightly, and most reversible inhibitors bind in the active site of enzymes, it is unsurprising that some of these inhibitors are strikingly similar in structure to the substrates of their targets. Inhibitors of

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can catalyse the decarboxylation of DFMO instead of ornithine (see the "DFMO inhibitor mechanism" diagram). However, this decarboxylation reaction is followed by the elimination of a fluorine atom, which converts this catalytic intermediate into a conjugated

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Multi-substrate analogue inhibitors are high affinity selective inhibitors that can be prepared for enzymes that catalyse reactions with more than one substrate by capturing the binding energy of each of those substrate into one molecule. For example, in the

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are often enzyme inhibitors that have evolved for use as toxic agents against predators, prey, and competing organisms. These natural toxins include some of the most poisonous substances known. Artificial inhibitors are often used as drugs, but can also be

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Sibille E, Bana E, Chaouni W, Diederich M, Bagrel D, Chaimbault P (November 2012). "Development of a matrix-assisted laser desorption/ionization-mass spectrometry screening test to evidence reversible and irreversible inhibitors of CDC25 phosphatases".

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cofactor together to produce thioglycinamide ribonucleotide dideazafolate (TGDDF), or enzymatically from the natural GAR substrate to yield GDDF. Here the subnanomolar dissociation constant (KD) of TGDDF was greater than predicted presumably due to

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Enzyme inactivation is generally explained as a chemical process involving several phenomena like aggregation, dissociation into subunits, or denaturation (conformational changes), which occur simultaneously during the inactivation of a specific

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leading to death and function for defence against predators or in hunting and capturing prey. Some of these natural inhibitors, despite their toxic attributes, are valuable for therapeutic uses at lower doses. An example of a neurotoxin are the

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are followed. However, at higher concentrations, the second inhibitory site becomes occupied, inhibiting the enzyme. Product inhibition (either the enzyme's own product, or a product to an enzyme downstream in its metabolic pathway) is often a

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The binding and inactivation steps of this reaction are investigated by incubating the enzyme with inhibitor and assaying the amount of activity remaining over time. The activity will be decreased in a time-dependent manner, usually following

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gives the rate of inactivation at this concentration of inhibitor. This is done at several different concentrations of inhibitor. If a reversible EI complex is involved the inactivation rate will be saturable and fitting this curve will give

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relating to the affinity of the enzyme for the substrate should in most cases relate to potential changes in the binding site of the enzyme which would directly result from enzyme inhibitor interactions. As such a term similar to the delta

3226:. Here, accurate measurement of the mass of the unmodified native enzyme and the inactivated enzyme gives the increase in mass caused by reaction with the inhibitor and shows the stoichiometry of the reaction. This is usually done using a 2015:

While this terminology results in a simplified way of dealing with kinetic effects relating to the maximum velocity of the Michaelis–Menten equation, it highlights potential problems with the term used to describe effects relating to the

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Since irreversible inhibition often involves the initial formation of a non-covalent enzyme inhibitor (EI) complex, it is sometimes possible for an inhibitor to bind to an enzyme in more than one way. For example, in the figure showing

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term turns out to be higher than the initial term. To account for the possibly of activation as well the notation can then be rewritten replacing the inhibitor "I" with a modifier term (stimulator or inhibitor) denoted here as "X".

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of databases of diverse molecules using computers, which are then followed by experimental confirmation of binding of the virtual screening hits. Complementary approaches that can provide new starting points for inhibitors include

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and may spontaneously leave the enzyme, allowing the enzyme to resume its function. Reversible inhibitors produce different types of inhibition depending on whether they bind to the enzyme, the enzyme-substrate complex, or both.

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the substrate and inhibitor cannot bind to the enzyme at the same time. This usually results from the inhibitor having an affinity for the active site of an enzyme where the substrate also binds; the substrate and inhibitor

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protease, so it is important to inhibit the activity of trypsin in the pancreas to prevent the organ from digesting itself. One way in which the activity of trypsin is controlled is the production of a specific and potent

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of the chemical reaction catalysed by the enzyme. The designed inhibitor often closely resembles the substrate, except that the portion of the substrate that undergoes chemical reaction is replaced by a chemically stable

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is not based on a peptide and has no obvious structural similarity to a protein substrate. These non-peptide inhibitors can be more stable than inhibitors containing peptide bonds, because they will not be substrates for

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Irreversible inhibition is different from irreversible enzyme inactivation. Irreversible inhibitors are generally specific for one class of enzyme and do not inactivate all proteins; they do not function by destroying

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An enzyme inhibitor stops ("inhibits") this process, either by binding to the enzyme's active site (thus preventing the substrate itself from binding) or by binding to another site on the enzyme such that the enzyme's

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blocks its activity as a protective mechanism against uncontrolled catalysis. The N‑terminal peptide is cleaved (split) from the zymogen enzyme precursor by another enzyme to release an active enzyme.

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control helps maintain a steady concentration of ATP in the cell. However, metabolic pathways are not just regulated through inhibition since enzyme activation is equally important. With respect to PFK1,

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indistinguishable from competitive orthosteric inhibition) or alternatively stabilise binding of substrate to the enzyme but lock the enzyme in a conformation which is no longer catalytically active.

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value. This is because the amount of active enzyme at a given concentration of irreversible inhibitor will be different depending on how long the inhibitor is pre-incubated with the enzyme. Instead,

782: 48:(P). Bottom: by binding to the enzyme, inhibitor (I) blocks binding of substrate. Binding site shown in blue checkerboard, substrate as black rectangle, and inhibitor as green rounded rectangle. 2918:

or intermediate of an enzyme-catalysed reaction. This ensures that the inhibitor exploits the transition state stabilising effect of the enzyme, resulting in a better binding affinity (lower

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This rearrangement demonstrates that similar to the Michaelis–Menten equation, the maximal rate of reaction depends on the proportion of the enzyme population interacting with its substrate.

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of the enzyme in an inhibitor/enzyme complex to show how the molecule is binding to the active site, allowing changes to be made to the inhibitor to optimise binding in a process known as

2515: 6551:"Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites" 5306:

Walsh R, Martin E, Darvesh S (May 2007). "A versatile equation to describe reversible enzyme inhibition and activation kinetics: modeling beta-galactosidase and butyrylcholinesterase".

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advantages gained and/or positive interactions acquired through the atoms linking the components. MAIs have also been observed to be produced in cells by reactions of pro-drugs such as

6488: 3699:. A less common class of toxins are toxic enzymes: these act as irreversible inhibitors of their target enzymes and work by chemically modifying their substrate enzymes. An example is 1631:

from 100% inhibition of substrate turn over to no inhibition. To account for this the equation can be easily modified to allow for different degrees of inhibition by including a delta

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Irreversible inhibitors bind to the enzyme's binding site then undergo a chemical reaction to form a covalent enzyme-inhibitor complex (EI*). Binding site in blue, inhibitor in green.

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The most common uses for enzyme inhibitors are as drugs to treat disease. Many of these inhibitors target a human enzyme and aim to correct a pathological condition. For instance,

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Enzyme inhibitors play an important role in all cells, since they are generally specific to one enzyme each and serve to control that enzyme's activity. For example, enzymes in a

6709:"Herpes simplex virus type 1 and human DNA polymerase interactions with 2'-deoxyguanosine 5'-triphosphate analogs. Kinetics of incorporation into DNA and induction of inhibition" 2625:

The effects of different types of reversible enzyme inhibitors on enzymatic activity can be visualised using graphical representations of the Michaelis–Menten equation, such as

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of all protein structure, but this is a non-specific effect. Similarly, some non-specific chemical treatments destroy protein structure: for example, heating in concentrated

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that inhibit upstream enzymes that produce those metabolites. This provides a negative feedback loop that prevents over production of metabolites and thus maintains cellular

4878: 3370:, a highly electrophilic species. This reactive form of DFMO then reacts with either a cysteine or lysine residue in the active site to irreversibly inactivate the enzyme. 421:

In contrast to irreversible inhibitors, reversible inhibitors generally do not undergo chemical reactions when bound to the enzyme and can be easily removed by dilution or

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Kinetic mechanisms for reversible inhibition. Substrate (S) binding to enzyme (E) in blue, catalysis releasing product (P) in red, inhibitor (I) binding to enzyme in green.

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that can be analysed using a mass spectrometer. The peptide that changes in mass after reaction with the inhibitor will be the one that contains the site of modification.

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hibitors) which are produced by animals to protect against inappropriate enzyme activation and by plants to prevent predation. Another class of inhibitor proteins is the

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Butterworth JF, IV, Mackey DC, Wasnick JD, eds. (2013). "Chapter 12. Cholinesterase Inhibitors & Other Pharmacologic Antagonists to Neuromuscular Blocking Agents.".

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Gentry BG, Bogner E, Drach JC (January 2019). "Targeting the terminase: An important step forward in the treatment and prophylaxis of human cytomegalovirus infections".

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Stone SR, Morrison JF (February 1986). "Mechanism of inhibition of dihydrofolate reductases from bacterial and vertebrate sources by various classes of folate analogs".

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Rozwarski DA, Grant GA, Barton DH, Jacobs WR, Sacchettini JC (January 1998). "Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis".

8875: 3497:(PFK1). When ATP levels rise, ATP binds an allosteric site in PFK1 to decrease the rate of the enzyme reaction; glycolysis is inhibited and ATP production falls. This 8088:

Goldstein I, Burnett AL, Rosen RC, Park PW, Stecher VJ (January 2019). "The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction".

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Gehringer M, Laufer SA (June 2019). "Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology".

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are bound in its active site. The top molecule is bound reversibly, but the lower one is bound covalently as it has reacted with an amino acid residue through its

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Holmes CF, Maynes JT, Perreault KR, Dawson JF, James MN (November 2002). "Molecular enzymology underlying regulation of protein phosphatase-1 by natural toxins".

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is the observed pseudo-first order rate of inactivation (obtained by plotting the log of % activity versus time) and is the concentration of inhibitor. The

3995:(AChE) is an enzyme found in animals, from insects to humans. It is essential to nerve cell function through its mechanism of breaking down the neurotransmitter 3258:

Chemical mechanism for irreversible inhibition of ornithine decarboxylase by DFMO. Pyridoxal 5'-phosphate (Py) and enzyme (E) are not shown. Adapted from Poulin

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Gohlke H, Klebe G (August 2002). "Approaches to the description and prediction of the binding affinity of small-molecule ligands to macromolecular receptors".

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bind to an enzyme, and this type of inhibition can therefore not be readily reversed. Irreversible inhibitors often contain reactive functional groups such as

3852:, which causes an erection. Since the drug decreases the activity of the enzyme that halts the signal, it makes this signal last for a longer period of time. 3345:

is an unusual type of irreversible inhibition where the enzyme converts the inhibitor into a reactive form in its active site. An example is the inhibitor of

8779: 7496:"A Systematic Review and Meta-Analysis of the Effectiveness of Acetylcholinesterase Inhibitors and Memantine in Treating the Cognitive Symptoms of Dementia" 5604:

Inglese J, Blatchly RA, Benkovic SJ (May 1989). "A multisubstrate adduct inhibitor of a purine biosynthetic enzyme with a picomolar dissociation constant".

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Kinetic mechanism for irreversible inhibition. Substrate binding in blue, catalysis in red, inhibitor binding in green, inactivation reaction in dark green.

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Cleland WW (February 1963). "The kinetics of enzyme-catalysed reactions with two or more substrates or products. II. Inhibition: nomenclature and theory".

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DeFrates LJ, Hoehns JD, Sakornbut EL, Glascock DG, Tew AR (January 2005). "Antimuscarinic intoxication resulting from the ingestion of moonflower seeds".

223:, meaning that only a minute amount of the inhibitor is required to inhibit the enzyme. A low concentration of the enzyme inhibitor reduces the risk for 6426:

Loo JA, DeJohn DE, Du P, Stevenson TI, Ogorzalek Loo RR (July 1999). "Application of mass spectrometry for target identification and characterization".

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figure above. As this drug resembles the peptide that is the substrate of the HIV protease, it competes with the substrate in the enzyme's active site.

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process, the first step of which is often the discovery of a new enzyme inhibitor. There are two principle approaches of discovering these inhibitors.

2231:, in which the inhibitor is titrated into a solution of enzyme and the heat released or absorbed is measured. However, the other dissociation constant 5569:

Schiffer CF, Burke JF, Besarab A, Lasker N, Simenhoff ML (January 1977). "Amylase/creatinine clearance fraction in patients on chronic hemodialysis".

7062: 2238:' is difficult to measure directly, since the enzyme-substrate complex is short-lived and undergoing a chemical reaction to form the product. Hence, 10115: 8336: 3323:(see the "DFP reaction" diagram). The enzyme hydrolyses the phosphorus–fluorine bond, but the phosphate residue remains bound to the serine in the 2220:' are the dissociation constants of the inhibitor for the enzyme and to the enzyme-substrate complex, respectively. The enzyme-inhibitor constant 2185:

Lineweaver–Burk diagrams of different types of reversible enzyme inhibitors. The arrow shows the effect of increasing concentrations of inhibitor.

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of large libraries of structurally diverse compounds to identify hit molecules that bind to the enzyme. This method has been extended to include

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An example of the structural similarity of some inhibitors to the substrates of the enzymes they target is seen in the figure comparing the drug

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Traditionally reversible enzyme inhibitors have been classified as competitive, uncompetitive, or non-competitive, according to their effects on

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may be inhibited by molecules produced later in the pathway, thus curtailing the production of molecules that are no longer needed. This type of

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Inglese J, Benkovic SJ (1991). "Multisubstrate Adduct Inhibitors of Glycinamide Ribonucleotide Transformylase: Synthetic and Enzyme Generated".

1890: 1750: 6983: 495:. Competitive inhibitors are often similar in structure to the real substrate (see for example the "methotrexate versus folate" figure in the 9994: 8358:

Zhang L, He J, Bai L, Ruan S, Yang T, Luo Y (July 2021). "Ribosome-targeting antibacterial agents: Advances, challenges, and opportunities".

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Lew W, Chen X, Kim CU (June 2000). "Discovery and development of GS 4104 (oseltamivir): an orally active influenza neuraminidase inhibitor".

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rather than cleaved. A large number of AChE inhibitors are used in both medicine and agriculture. Reversible competitive inhibitors, such as

2450:{\displaystyle V={\frac {V_{max}}{\alpha K_{m}+\alpha ^{\prime }}}={\frac {(1/\alpha ^{\prime })V_{max}}{(\alpha /\alpha ^{\prime })K_{m}+}}} 4541:

Boon L, Ugarte-Berzal E, Vandooren J, Opdenakker G (April 2020). "Protease propeptide structures, mechanisms of activation, and functions".

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Enzyme inhibitors are found in nature and also produced artificially in the laboratory. Naturally occurring enzyme inhibitors regulate many

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that inactivates ribosomes. Since ricin is a catalytic irreversible inhibitor, this allows just a single molecule of ricin to kill a cell.

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Although many natural toxins are secondary metabolites, these poisons also include peptides and proteins. An example of a toxic peptide is

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Abal M, Andreu JM, Barasoain I (June 2003). "Taxanes: microtubule and centrosome targets, and cell cycle dependent mechanisms of action".

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Fischer PM (October 2003). "The design, synthesis and application of stereochemical and directional peptide isomers: a critical review".

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In drug design it is important to consider the concentrations of substrates to which the target enzymes are exposed. For example, some

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Schematics for reversible inhibition. Binding site in blue, substrate in black, inhibitor in green, and allosteric site in light green.

4905: 3635:. Inhibition of this enzyme causes an uncontrolled increase in the acetylcholine neurotransmitter, muscular paralysis and then death. 2521: 9525: 6439: 600:

of inhibition is unchanged, and for uncompetitive (also called anticompetitive) inhibition the degree of inhibition increases with .

450:(the concentration of substrate resulting in half maximal enzyme activity) as the concentration of the enzyme's substrate is varied. 8231:

Buynak JD (September 2007). "Cutting and stitching: the cross-linking of peptidoglycan in the assembly of the bacterial cell wall".

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Bischoff K (October 2001). "The toxicology of microcystin-LR: occurrence, toxicokinetics, toxicodynamics, diagnosis and treatment".

6912:"Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase: a template for drug design" 6760:"Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase: a template for drug design" 6123:

Bogoyevitch MA, Barr RK, Ketterman AJ (December 2005). "Peptide inhibitors of protein kinases-discovery, characterisation and use".

3821:, an enzyme that is potently inhibited by methotrexate. Methotrexate blocks the action of dihydrofolate reductase and thereby halts 2940:

However, not all inhibitors are based on the structures of substrates. For example, the structure of another HIV protease inhibitor

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substrate A for the first binding site, but be a non-competitive inhibitor with respect to substrate B in the second binding site.

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Recommendations of the Nomenclature Committee of the International Union of Biochemistry (NC-IUB) on enzyme inhibition terminology

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Hiratake J (2005). "Enzyme inhibitors as chemical tools to study enzyme catalysis: rational design, synthesis, and applications".

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as the enzyme "clamps down" around the inhibitor molecule. Examples of slow-binding inhibitors include some important drugs, such

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for access to the enzyme's active site. This type of inhibition can be overcome by sufficiently high concentrations of substrate (

6379:"Comparison of methods for analyzing kinetic data from mechanism-based enzyme inactivation: application to nitric oxide synthase" 2790:

TGDDF/GDDF multi-substrate adduct inhibitor. Substrate analogue in black, cofactor analogue in blue, non-cleavable linker in red.

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Polakovič M, Vrabel P, Báleš V (January 1998). "Approaches for improved identification of mechanisms of enzyme inactivation".

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Drugs are also used to inhibit enzymes needed for the survival of pathogens. For example, bacteria are surrounded by a thick

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with the enzyme such that the enzyme is inhibited until the chemical bond is broken. By contrast, reversible inhibitors bind

8869: 2677:' accurately from such plots, it is advisable to estimate these constants using more reliable nonlinear regression methods. 7142: 5049: 4506:

Shapiro R, Vallee BL (February 1991). "Interaction of human placental ribonuclease with placental ribonuclease inhibitor".

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Holdgate GA (July 2001). "Making cool drugs hot: isothermal titration calorimetry as a tool to study binding energetics".

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Le Calvez PB, Scott CJ, Migaud ME (December 2009). "Multisubstrate adduct inhibitors: drug design and biological tools".

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biosynthesis is selectively toxic to rapidly growing cells, therefore methotrexate is often used in cancer chemotherapy.

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an enzyme having two competing substrate-binding sites. At low substrate, the high-affinity site is occupied and normal

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Tan S, Evans R, Singh B (March 2006). "Herbicidal inhibitors of amino acid biosynthesis and herbicide-tolerant crops".

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Agbowuro AA, Huston WM, Gamble AB, Tyndall JD (July 2018). "Proteases and protease inhibitors in infectious diseases".

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but by specifically altering the active site of their target. For example, extremes of pH or temperature usually cause

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Tseng SJ, Hsu JP (August 1990). "A comparison of the parameter estimating procedures for the Michaelis-Menten model".

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Irreversible inhibitors display time-dependent inhibition and their potency therefore cannot be characterised by an IC

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generally possess higher affinity for the enzyme compared to the substrate, and therefore are effective inhibitors.

341:("alternative" orientation) inhibitors. The mechanisms of allosteric inhibition are varied and include changing the 9854: 2460:

where the modifying factors α and α' are defined by the inhibitor concentration and its two dissociation constants

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Mixed-type inhibitors bind to both E and ES, but their affinities for these two forms of the enzyme are different (

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Physiological enzyme inhibition can also be produced by specific protein inhibitors. This mechanism occurs in the

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Lindquist RN (October 2013). "The design of enzyme inhibitors: Transition state analogues.". In Ariëns EJ (ed.).

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Plant Protease Inhibitors: Significance in Nutrition, Plant Protection, Cancer Prevention and Genetic Engineering

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or three-dimensional shape) of the enzyme so that the affinity of the substrate for the active site is reduced.

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Voshavar C (2019). "Protease Inhibitors for the Treatment of HIV/AIDS: Recent Advances and Future Challenges".

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Li G, Jing X, Pan, Zhang P, De Clercq E (2021). "Antiviral Classification". In Bamford D, Zuckerman MA (eds.).

4160: 3845: 3632: 7290: 4234:– a type of enzyme inhibitor that mimics the transition state of the chemical reaction catalysed by the enzyme 1556: 1476: 429:

that form a chemical bond with the enzyme, but the bond can be cleaved so the inhibition is fully reversible.

10304: 9908: 9742: 9503: 4352: 4156: 7193:

Okar DA, Lange AJ (1999). "Fructose-2,6-bisphosphate and control of carbohydrate metabolism in eukaryotes".

673:. The inhibitor affects substrate binding by increasing the enzyme's affinity for the substrate (decreasing 10432: 9980: 9941: 9933: 7467:

Hostettmann K, Borloz A, Urbain A, Marston A (2006). "Natural Product Inhibitors of Acetylcholinesterase".

3298:

with the lower molecule of an inhibitor bound irreversibly and the upper one reversibly. Created from Bond

8268:"Selective toxicity of antibacterial agents-still a valid concept or do we miss chances and ignore risks?" 8010:

McLornan DP, Pope JE, Gotlib J, Harrison CN (August 2021). "Current and future status of JAK inhibitors".

7044: 4115:

Robots are used for the high-throughput screening of chemical libraries to discover new enzyme inhibitors.

3758:

As of 2017, an estimated 29% of approved drugs are enzyme inhibitors of which approximately one-fifth are

3531:

destabilising the transition state. Other examples of physiological enzyme inhibitor proteins include the

567:

will remain the same as the actual binding of the substrate, by definition, will still function properly.

152:

produced by animals or plants are enzyme inhibitors that block the activity of crucial enzymes in prey or

9837: 9827: 9809: 9750: 9654: 9376:

Perez O, Pena J, Fernandez-Vega V, Scampavia L, Spicer T (2019). "Chapter 4: High Throughput Screening".

6810: 3231: 3093: 526: 9401:

Scarpino A, Ferenczy GG, Keserű GM (2020). "Covalent Docking in Drug Discovery: Scope and Limitations".

8316: 6076:"Small molecule substrate phosphorylation site inhibitors of protein kinases: approaches and challenges" 163:

are enzyme inhibitors that inhibit an aberrant human enzyme or an enzyme critical for the survival of a

10442: 10070: 9691: 9633: 9596: 9545: 5266:

Walsh R, Martin E, Darvesh S (December 2011). "Limitations of conventional inhibitor classifications".

3316: 3132:/ parameter is valid as long as the inhibitor does not saturate binding with the enzyme (in which case 3069: 2987: 545: 277:

In addition to small molecules, some proteins act as enzyme inhibitors. The most prominent example are

200: 8174:"Breaking down the cell wall: Strategies for antibiotic discovery targeting bacterial transpeptidases" 2925:) than substrate-based designs. An example of such a transition state inhibitor is the antiviral drug 10405: 10392: 10379: 10366: 10353: 10340: 10327: 10289: 9957: 9780: 4261:

Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists

4231: 4215: 4147: 4140: 4139:

that resembles the transition state. Since the enzyme has evolved to stabilise the transition state,

4100: 3503: 2846: 617: 117: 9646: 7164:

Orencio-Trejo M, Utrilla J, Fernández-Sandoval MT, Huerta-Beristain G, Gosset G, Martinez A (2010).

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in humans. Hence the discovery and refinement of enzyme inhibitors is an active area of research in

10299: 10253: 10196: 9913: 9775: 7775:

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Thapa S, Lv M, Xu H (2017). "Acetylcholinesterase: A Primary Target for Drugs and Insecticides".

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de Leuw P, Stephan C (April 2018). "Protease inhibitor therapy for hepatitis C virus-infection".

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Walsh CT (1984). "Suicide substrates, mechanism-based enzyme inactivators: recent developments".

5711:"Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124" 3968: 3849: 3818: 3684:

and is a known carcinogen that can also cause acute liver haemorrhage and death at higher doses.

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Hartley RW (November 1989). "Barnase and barstar: two small proteins to fold and fit together".

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Szedlacsek SE, Duggleby RG (1995). "[6] Kinetics of slow and tight-binding inhibitors".

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3783: 3654: 3650: 3493:. A key step for the regulation of glycolysis is an early reaction in the pathway catalysed by 3482: 3328: 2867: 459: 294: 8976: 7865: 5101:"Enzyme-Inhibitor Interactions and a Simple, Rapid Method for Determining Inhibition Modality" 4729: 4588: 10222: 10141: 10075: 9898: 7826:

Hartley MR, Lord JM (September 2004). "Cytotoxic ribosome-inactivating lectins from plants".

7165: 7085: 6162: 4190:. This test and improve cycle is repeated until a sufficiently potent inhibitor is produced. 4080: 3976: 3787: 3507: 3268: 2630: 2190: 622: 609: 584:

effect where the inhibitor binds to a different site on an enzyme. Inhibitor binding to this

251:

Enzyme inhibitors are a chemically diverse set of substances that range in size from organic

232: 220: 97: 4909: 3848:. This signalling molecule triggers smooth muscle relaxation and allows blood flow into the 10294: 7595: 6338:"Profiling the specific reactivity of the proteome with non-directed activity-based probes" 5814:

Avendano C, Menendez JC (June 2015). "Chapter 2.5: Inhibitors of Dihydrofolate Reductase".

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Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems

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Animals and plants have evolved to synthesise a vast array of poisonous products including

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for predicting the binding orientation and affinity of an inhibitor for an enzyme such as

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Santos R, Ursu O, Gaulton A, Bento AP, Donadi RS, Bologa CG, et al. (January 2017).

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Radzicka A, Wolfenden R (1995). "Transition state and multisubstrate analog inhibitors".

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the inhibitor binds only to the enzyme-substrate complex. This type of inhibition causes

199:. Since anti-pathogen inhibitors generally target only one enzyme, such drugs are highly 192: 188: 109: 85: 45: 7599: 6888: 5726: 5679: 5473: 5364:. Eli Lilly & Company and the National Center for Advancing Translational Sciences. 4645: 4630:"Analysis of equilibrium binding of an orthosteric tracer and two allosteric modulators" 4259:

Copeland RA (March 2013). "Why Enzymes as Drug Targets? Enzyme are Essential for Life".

3335:

of neurons, and consequently is a potent neurotoxin, with a lethal dose of less than 100

10191: 9601: 9472: 9445: 9426: 9358: 9304: 9279: 9140: 9061: 9048: 9028: 8957: 8845: 8820: 8710: 8667: 8654: 8629: 8605: 8580: 8561: 8518: 8460: 8427: 8402: 8383: 8292: 8267: 8201: 8113: 8035: 7987: 7962: 7934: 7909: 7803: 7776: 7752: 7725: 7568: 7525: 7218: 6938: 6911: 6910:

Saravanamuthu A, Vickers TJ, Bond CS, Peterson MR, Hunter WN, Fairlamb AH (July 2004).

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Saravanamuthu A, Vickers TJ, Bond CS, Peterson MR, Hunter WN, Fairlamb AH (July 2004).

6684: 6667: 6475:

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6451: 6403: 6378: 6227: 6100: 6075: 5981: 5956: 5899: 5793: 5745: 5710: 5130: 4800: 4775: 4664: 4629: 4566: 4483: 4456: 4323: 4298: 3803: 3342: 593: 518:

to decrease (maximum velocity decreases as a result of removing activated complex) and

433: 263: 9414: 8977:"Major Synthetic Routes for Modern Herbicide Classes and Agrochemical Characteristics" 8910: 8506: 8023: 7607: 7238:

Fundamentals of enzymology : the cell and molecular biology of catalytic proteins

7163: 6822: 6725: 6708: 6567: 6550: 6354: 6337: 6283: 5652: 5481: 4408: 3171: 2999: 2841:, a potent Multi-substrate Adduct Inhibitor (MAI) to glycinamide ribonucleotide (GAR) 2798: 642:

Competitive inhibitors can bind to E, but not to ES. Competitive inhibition increases

10065: 9871: 9477: 9430: 9418: 9381: 9362: 9350: 9309: 9260: 9225: 9190: 9144: 9132: 9089: 9066: 8992: 8949: 8914: 8850: 8787: 8758: 8733: 8702: 8671: 8659: 8610: 8553: 8522: 8510: 8475: 8465: 8432: 8387: 8375: 8328: 8297: 8248: 8205: 8193: 8154: 8105: 8070: 8039: 8027: 7992: 7939: 7873: 7843: 7808: 7757: 7704: 7700: 7673: 7646: 7611: 7560: 7517: 7449: 7414: 7377: 7352: 7329: 7325: 7282: 7241: 7210: 7173: 7134: 7093: 7052: 7025: 6973: 6943: 6892: 6855: 6826: 6791: 6748: 6730: 6689: 6648: 6644: 6613: 6603: 6599: 6572: 6528: 6478: 6443: 6408: 6359: 6316: 6287: 6250: 6219: 6170: 6140: 6105: 6056: 6021: 5986: 5934: 5891: 5856: 5819: 5785: 5750: 5691: 5621: 5586: 5551: 5541: 5537: 5508: 5485: 5439: 5435: 5404: 5365: 5323: 5283: 5243: 5218: 5193: 5157: 5122: 5079: 5041: 5012: 4979: 4951: 4868: 4843: 4839: 4805: 4737: 4696: 4669: 4596: 4570: 4558: 4523: 4488: 4435: 4412: 4360: 4328: 4272: 4182:

can be used to assist in the optimisation process. New inhibitors are used to obtain

4175: 4151: 4036: 3944: 3908: 3874: 3744: 3692: 3669: 3645: 3560: 3527: 3458: 3380: 3304: 3223: 3197: 3097: 3089: 2724: 204: 129: 125: 73: 8714: 8698: 8133:"Erectile dysfunction: from biochemical pharmacology to advances in medical therapy" 8117: 7572: 7529: 7222: 6455: 6231: 5903: 5797: 5134: 3723:

The coenzyme folic acid (top) compared to the anti-cancer drug methotrexate (bottom)

2735:

Slow-tight inhibition occurs when the initial enzyme–inhibitor complex EI undergoes

379: 367: 10237: 10206: 10134: 10100: 10095: 10045: 9606: 9467: 9457: 9410: 9340: 9299: 9291: 9252: 9217: 9182: 9122: 9056: 9040: 8984: 8961: 8941: 8906: 8840: 8832: 8694: 8649: 8641: 8600: 8592: 8565: 8545: 8502: 8455: 8422: 8414: 8367: 8287: 8279: 8240: 8185: 8144: 8097: 8062: 8053:

McGuire JJ (2003). "Anticancer antifolates: current status and future directions".

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Auld DS, Lovell S, Thorne N, Lea WA, Maloney DJ, Shen M, et al. (March 2010).

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Biochimica et Biophysica Acta (BBA) - Specialized Section on Enzymological Subjects

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Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research

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will decrease due to the inability for the reaction to proceed as efficiently, but

216: 89: 9537: 9529: 8549: 7978: 4554: 608:

Reversible inhibition can be described quantitatively in terms of the inhibitor's

432:

Reversible inhibitors are generally categorized into four types, as introduced by

10284: 10268: 10181: 10020: 9876: 9683: 9295: 9256: 9127: 9110: 8988: 8418: 8189: 7839: 7051:(Third ed.). Philadelphia, Pa.: Elsevier Health Sciences. pp. 153–155. 6215: 6136: 5319: 4654: 4044: 3324: 2991: 2715: 2637:. An illustration is provided by the three Lineweaver–Burk plots depicted in the 2254: 2246: 613: 585: 549: 422: 346: 65: 9972: 8645: 7126: 6633:

Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology

5972: 5687: 5033: 5008: 4791: 4111: 2883:(DHFR) are prominent examples. Other examples of these substrate mimics are the 2808:

with substrate binding sites located in enzyme labelled as S2, S1, S1', and S2'.

10322: 10263: 10085: 10050: 9729: 9716: 9623: 9345: 9328: 9186: 8596: 8283: 8101: 7774: 7480: 7410: 6169:(Sixth ed.). Oxford, United Kingdom: Oxford University Press. p. 95. 5930: 5852: 5715:

Proceedings of the National Academy of Sciences of the United States of America

5357: 4225: 4207: 4096: 4020: 4016: 3948: 3916: 3748: 3696: 3695:(discussed in the "metabolic regulation" section above) that are found in some 3661: 3572: 3571:, peptides and proteins that can act as inhibitors. Natural toxins are usually 3552: 3462: 2953: 2900: 2249:

under various substrate and inhibitor concentrations, and fitting the data via

2227:

can be measured directly by various methods; one especially accurate method is

735:'). Thus, mixed-type inhibitors affect substrate binding (increase or decrease 481:

will increase as it takes a higher concentration of the substrate to reach the

474:

remains constant), i.e., by out-competing the inhibitor. However, the apparent

252: 228: 224: 137: 8945: 8836: 8479: 7278: 5781: 5582: 4268: 2652:. In the bottom diagram the non-competitive inhibition lines intersect on the 536:

which indicates a higher binding affinity). Uncompetitive inhibition is rare.

10421: 10227: 10186: 10110: 10035: 10025: 9859: 8066: 7642: 7445: 6524: 6052: 6017: 5117: 5100: 4228:– an enzyme inhibitor that is used to interfere with cell growth and division 4222:

that uses covalent enzyme inhibitors as reporters to monitor enzyme activity.

4028: 3996: 3891: 3752: 3751:

enzyme. This inhibition in turn suppresses the production of proinflammatory

3636: 3612: 3588: 3469:

acting as inhibitors and enhancers for the enzymes in that same pathway. The

3438: 3375: 3295: 3201: 3045: 2934: 2845:

was prepared synthetically by linking analogues of the GAR substrate and the

2641:

figure. In the top diagram the competitive inhibition lines intersect on the

659:

Uncompetitive inhibitors bind to ES. Uncompetitive inhibition decreases both

656:(the inhibitor does not hamper catalysis in ES because it cannot bind to ES). 649:(i.e., the inhibitor interferes with substrate binding), but does not affect 436:

in 1963. They are classified according to the effect of the inhibitor on the

403: 113: 7691:

Savage GP, Morrison SC (2003). "Trypsin inhibitors.". In Caballero B (ed.).

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Ganguly AK, Alluri SS (12 September 2021). "Chapter 2: Enzyme Inhibitors".

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Walsh R (May 2012). "Alternative perspectives of enzyme kinetic modeling".

5327: 5287: 5126: 5045: 4847: 4809: 4673: 4562: 4492: 4416: 4332: 4314: 4076: 4056: 3810: 3779: 3688: 3596: 3426: 3350: 3272: 3254: 3101: 2904: 2005:{\displaystyle V_{\max 1}-(V_{\max 1}-V_{\max 2}){\cfrac {\ce {}}{+K_{x}}}} 1865:{\displaystyle V_{\max 1}-(V_{\max 1}-V_{\max 2}){\cfrac {\ce {}}{+K_{i}}}} 322: 298: 240: 236: 184: 180: 9222:

10.1002/1521-3773(20020802)41:15<2644::AID-ANIE2644>3.0.CO;2-O

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Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

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Polito L, Bortolotti M, Battelli MG, Calafato G, Bolognesi A (June 2019).

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to the enzyme and to the enzyme-substrate complex, and its effects on the

10400: 10335: 10171: 10040: 9706: 9462: 9446:"Mechanisms of Proteolytic Enzymes and Their Inhibition in QM/MM Studies" 7925: 5590: 4171: 4167: 4032: 4024: 3960: 3923: 3767: 3719: 3708: 3681: 3677: 3673: 3668:

mushroom. This is a potent enzyme inhibitor, in this case preventing the

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10.1002/(SICI)1098-1128(199907)19:4<307::AID-MED4>3.0.CO;2-2

5617: 4519: 10030: 9052: 5279: 4219: 4092: 4084: 4068: 3932: 3903: 3899: 3895: 3837: 3826: 3814: 3732: 3616: 3603: 3577: 3474: 3470: 3422: 3061: 3025: 2941: 2823: 581: 411: 325:

of inhibitors on enzymes is most commonly the same site that binds the

310: 160: 8371: 8244: 7556: 7512: 7495: 7021: 6752: 6091: 5887: 4007:. This is somewhat unusual among neurotransmitters as most, including 3878: 3755:

and thus aspirin may be used to reduce pain, fever, and inflammation.

3404:

processes and are essential for life. In addition, naturally produced

3327:, deactivating it. Similarly, DFP also reacts with the active site of 3308: 32: 10374: 10348: 9799: 9508:, Database of enzymes giving lists of known inhibitors for each entry 7777:"Intracellular Transport and Cytotoxicity of the Protein Toxin Ricin" 7170:

Biosystems Engineering II: Linking Cellular Networks and Bioprocesses

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Enzyme Kinetics and Mechanism Part D: Developments in Enzyme Dynamics

4736:(First ed.). Boca Raton, FL: Garland Science. pp. 531–580. 4052: 4048: 4040: 4008: 3988: 3972: 3822: 3795: 3665: 3607: 3430: 3418: 3414: 3401: 3354: 3346: 3280: 3227: 3077: 3037: 2946: 2896: 2855: 2805: 172: 105: 9512: 9044: 4540: 3547: 2767:) rate constants for inhibitor association with kinetics similar to 529:

and the effective elimination of the ES complex thus decreasing the

7262: 4695:(Fifth ed.). Oxford, UK: Oxford University Press. p. 90. 4201: 4012: 3956: 3928: 3775: 3640: 3628: 3514: 3498: 3490: 3332: 3235: 3081: 3073: 3057: 3021: 3013: 2892: 2851: 1734:{\displaystyle V_{\max }-\Delta V_{\max }{\cfrac {\ce {}}{+K_{i}}}} 690:

Non-competitive inhibitors have identical affinities for E and ES (

208: 203:

and generally produce few side effects in humans, provided that no

196: 176: 164: 153: 145: 141: 57: 8581:"Approved HIV reverse transcriptase inhibitors in the past decade" 4627: 553:

of inhibition depends only on the concentration of the inhibitor.

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pesticides are also examples of reversible AChE inhibitors. The

2580:{\displaystyle \alpha ^{\prime }=1+{\frac {}{K_{i}^{\prime }}}.} 10387: 10157: 9638: 9243:

Koppitz M, Eis K (June 2006). "Automated medicinal chemistry".

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can also result from the inhibition of receptors; for example,

3624: 3620: 3556: 3405: 3065: 3049: 3029: 2980: 2859: 2590:

Thus, in the presence of the inhibitor, the enzyme's effective

2166:{\displaystyle K_{m1}-(K_{m1}-K_{m2}){\cfrac {\ce {}}{+K_{x}}}} 278: 207:

enzyme is found in humans. (This is often the case, since such

149: 61: 37: 8317:"How do antibiotics kill bacterial cells but not human cells?" 8131:

Maggi M, Filippi S, Ledda F, Magini A, Forti G (August 2000).

7466: 6961:

Pereira DM, Andrade C, Valentão P, Andrade PB (October 2017).

4263:(Second ed.). John Wiley & Sons, Inc. pp. 1–23. 4170:

to high affinity binders that efficiently inhibit the enzyme.

3517:, which synthesises many digestive precursor enzymes known as 3052:. The residues modified are those with side chains containing 10361: 9923: 9015:

Chapter 10.2.1: Sulfonylurea acetolactate synthase inhibitors

8819:

Farmakidis C, Pasnoor M, Dimachkie MM, Barohn RJ (May 2018).

7828:

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Knight R, Khondoker M, Magill N, Stewart R, Landau S (2018).

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The Molecules of Life : Physical and Chemical Principles

4088: 3727: 3700: 3581: 3367: 3234:

involves digestion of the native and modified protein with a

2784: 525:

to decrease (due to better binding efficiency as a result of

212: 168: 92:

a specific chemical reaction by binding the substrate to its

8780:"Classification and Uses of Organophosphates and Carbamates" 7493: 6549:

Poulin R, Lu L, Ackermann B, Bey P, Pegg AE (January 1992).

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are examples of metabolites that are allosteric activators.

10015: 8983:. Springer Science & Business Media. pp. 179–195. 7628: 6509: 5873: 5098: 4908:. NIH Center for Translational Therapeutics. Archived from 3860: 3291: 711:(i.e., it does not affect substrate binding) but decreases 414:. Multiple weak bonds between the inhibitor and the enzyme 140:. Enzyme inhibitors also control essential enzymes such as 77: 10126: 9173:

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and hence these inhibitors are used to treat a variety of

3762:

inhibitors. A notable class of kinase drug targets is the

3048:

groups react with amino acid side chains to form covalent

8087: 7586:

Vetter J (January 1998). "Toxins of Amanita phalloides".

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can be obtained through more complex analysis of the on (

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Another method that is widely used in these analyses is

96:, a specialized area on the enzyme that accelerates the 9086:

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The second way of discovering new enzyme inhibitors is

3104:

holding proteins together, releasing free amino acids.

2645:-axis, illustrating that such inhibitors do not affect 2129: 2109: 1968: 1948: 1828: 1808: 1697: 1677: 1583: 1563: 1503: 1483: 1398: 1378: 1302: 1269: 1219: 1199: 1081: 1034: 979: 960: 911: 892: 841: 821: 807: 788: 548:

the binding of the inhibitor to the enzyme reduces its

108:

of the reaction is blocked. Enzyme inhibitors may bind

9400: 7907: 6970:

Natural Products Targeting Clinically Relevant Enzymes

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4941: 4939: 4937: 4935: 4933: 4931: 4929: 4927: 4730:"Molecular Recognition: The Thermodynamics of Binding" 4543:

Critical Reviews in Biochemistry and Molecular Biology

3817:. Folic acid is the oxidised form of the substrate of 2132: 2112: 1971: 1951: 1831: 1811: 1700: 1680: 1586: 1566: 1506: 1486: 1401: 1381: 1305: 1272: 1222: 1202: 1084: 1037: 982: 963: 914: 895: 844: 824: 810: 791: 8786:. Amsterdam: Elsevier Academic Press. pp. 5–24. 8784:

Toxicology of Organophosphate and Carbamate Compounds

7396: 6477:. San Diego, Calif.: Elsevier Academic. p. 542. 5502: 5217:. Hoboken, N.J.: Wiley-Interscience. pp. 61–69. 5213:

Marangoni AG (2003). "Reversible Enzyme Inhibition".

4727: 4454: 2524: 2469: 2266: 2054: 1893: 1753: 1647: 1559: 1550:

fraction of the enzyme population bound by inhibitor

1479: 1470:

fraction of the enzyme population bound by substrate

780: 313:

peptide that binds to the active site of enzyme that

7768: 7726:"Ricin: An Ancient Story for a Timeless Plant Toxin" 7124: 6548: 6425: 6269: 5770:

Journal of Enzyme Inhibition and Medicinal Chemistry

5767: 4197: 3782:

are another notable example of drug enzyme targets.

3770:; their over-activation may result in cancer. Hence 3465:

through a pathway is often regulated by a pathway's

2903:(peptide mimic) protease inhibitor containing three 443:(maximum reaction rate catalysed by the enzyme) and 9567: 7431: 6335: 5708: 4924: 4430:Gualerzi CO, Brandi L, Fabbretti A, Pon CL (2013). 4039:and in anaesthesia to reverse muscle blockade. The 3844:, the enzyme that degrades the signalling molecule 2245:' is usually measured indirectly, by observing the 742:) and hamper catalysis in the ES complex (decrease 9380:. Boca Raton, Florida: CRC Press. pp. 47–69. 9088:. Boca Raton, Florida: CRC Press. pp. 29–68. 7960: 7863: 7157: 7125:Greathouse B, Zahra F, Brady MF (September 2021). 6589: 6310: 5305: 5265: 5183: 5181: 5179: 5177: 5175: 5173: 4999:Palmer T, Bonner PL (2007). "Enzyme inhibition.". 4860: 3680:. This toxin can contaminate water supplies after 2914:Enzyme inhibitors are often designed to mimic the 2579: 2509: 2449: 2165: 2004: 1864: 1733: 1619: 1539: 1456: 305:. A special case of protein enzyme inhibitors are 10002: 8684: 7090:Chemical Pesticides Mode of Action and Toxicology 6854:(1st ed.). Philadelphia, PA: W.B. Saunders. 6665: 6336:Adam GC, Cravatt BF, Sorensen EJ (January 2001). 5527: 5105:SLAS Discovery: Advancing Life Sciences R & D 3840:(Viagra). This compound is a potent inhibitor of 3230:mass spectrometer. In a complementary technique, 2929:; this drug mimics the planar nature of the ring 2663:. However, since it can be difficult to estimate 148:that, if left unchecked, may damage a cell. Many 10419: 9280:"Fragment-based approaches to enzyme inhibition" 8812: 7460: 5813: 5809: 5807: 5031: 4582: 4580: 4357:Functional Metabolism: Regulation and Adaptation 1934: 1918: 1899: 1794: 1778: 1759: 1669: 1653: 1445: 1370: 1357: 1179: 1021: 879: 798: 418:combine to produce strong and specific binding. 112:or irreversibly. Irreversible inhibitors form a 9443: 8974: 8578: 7949:Total enzyme targets of approved drugs = 29.45% 7910:"A comprehensive map of molecular drug targets" 7133:. Treasure Island (FL): StatPearls Publishing. 6666:Pick FM, McGartoll MA, Bray RC (January 1971). 6201: 6156: 6154: 5950: 5948: 5838: 5638: 5503:Dixon M, Webb EC, Thorne CJ, Tipton KF (1979). 5170: 5154:Physical Chemistry with Biological Applications 4821: 4819: 4432:Antibiotics: Targets, Mechanisms and Resistance 4254: 4252: 4250: 4248: 3353:(DFMO), which is an analogue of the amino acid 704:'). Non-competitive inhibition does not change 9526:"Symbolism and Terminology in Enzyme Kinetics" 9394: 8871:Morgan & Mikhail's Clinical Anesthesiology 8621: 8535: 8486: 8449: 8357: 8171: 8165: 7954: 7903: 7901: 7859: 7857: 7690: 6195: 5761: 5507:(3rd ed.). London: Longman. p. 126. 5206: 4945: 4448: 4390: 4388: 4346: 4344: 4342: 3672:enzyme from transcribing DNA. The algal toxin 2656:-axis, showing these inhibitors do not affect 219:.) Medicinal enzyme inhibitors often have low 10142: 9988: 9553: 9517:National Center for Biotechnology Information 9083: 8979:. In Böger P, Wakabayashi K, Hirai K (eds.). 8931: 8925: 8627: 8529: 8259: 8003: 7042: 7001: 6630: 6592:Kinetics of slow and tight-binding inhibitors 6073: 5957:"Enzymatic Transition States and Drug Design" 5867: 5804: 5455: 5453: 5421: 5301: 5299: 5297: 5261: 5259: 5073: 4769: 4767: 4765: 4577: 4505: 4166:Hits from any of the above approaches can be 3864:The structure of a complex between penicillin 3703:, an extremely potent protein toxin found in 2746:, which is time–dependent. The true value of 398:Reversible inhibitors attach to enzymes with 10116:Quantitative structure–activity relationship 9333:Bioorganic & Medicinal Chemistry Letters 9326: 9271: 9029:"Overview of herbicide mechanisms of action" 8678: 8224: 8081: 7235: 6741: 6503: 6419: 6151: 5997: 5945: 5349: 5069: 5067: 5025: 4998: 4816: 4680: 4621: 4423: 4292: 4290: 4288: 4245: 4073:3-phosphoshikimate 1-carboxyvinyltransferase 3947:are effective in treating viral infections. 3072:, see the "DFP reaction" diagram), and also 2774: 2619: 2189:An enzyme inhibitor is characterised by its 718:(i.e., inhibitor binding hampers catalysis). 680:) as well as hampering catalysis (decreases 262:Small molecule inhibitors include essential 9450:International Journal of Molecular Sciences 9277: 9207: 9102: 8890: 8771: 8727: 8634:Cold Spring Harbor Perspectives in Medicine 8351: 7898: 7854: 7825: 7717: 7693:Encyclopedia of Food Sciences and Nutrition 7487: 7168:. In Cordes M, Wittmann C, Krull R (eds.). 6809:Cohen JA, Oosterbaan RA, Berends F (1967). 4992: 4385: 4339: 4059:irreversibly inhibit acetylcholinesterase. 3778:are frequently used to treat malignancies. 3433:. Other artificial enzyme inhibitors block 2510:{\displaystyle \alpha =1+{\frac {}{K_{i}}}} 603: 10149: 10135: 9995: 9981: 9560: 9546: 9320: 9242: 7961:Kannaiyan R, Mahadevan D (December 2018). 7500:Dementia and Geriatric Cognitive Disorders 7346: 7127:"Acetylcholinesterase Inhibitors Toxicity" 7092:. Boca Raton: CRC Press. pp. 73–114. 6868: 6376: 6247:Chemical reagents for protein modification 6067: 6003: 5450: 5334: 5294: 5256: 5187: 5092: 5032:Delaune KP, Alsayouri K (September 2021). 4900: 4898: 4896: 4762: 4589:"Chapter 7.2.1: Competition and Allostery" 3943:Drugs that inhibit enzymes needed for the 3766:which are essential enzymes that regulate 3580:(taxol), an organic molecule found in the 2960: 2858:or enzyme inhibitor ligands (for example, 2045:should be appropriate in most situations: 9471: 9461: 9344: 9303: 9157: 9126: 9060: 8896: 8844: 8653: 8604: 8459: 8426: 8394: 8291: 8148: 7986: 7933: 7802: 7792: 7751: 7741: 7511: 7240:(3rd ed.). Oxford University Press. 7192: 7083: 6937: 6927: 6811:"[81] Organophosphorus compounds" 6785: 6775: 6724: 6683: 6566: 6544: 6542: 6402: 6353: 6099: 5980: 5744: 5734: 5212: 5116: 5064: 4799: 4773: 4663: 4653: 4586: 4482: 4472: 4322: 4285: 3676:is also a peptide and is an inhibitor of 3457:Enzyme inhibition is a common feature of 2720: 2176: 1620:{\displaystyle {\cfrac {\ce {}}{+K_{i}}}} 1540:{\displaystyle {\cfrac {\ce {}}{+K_{m}}}} 9162:. Vol. 5. Elsevier. pp. 24–80. 8630:"Antivirals Targeting the Neuraminidase" 8579:Li G, Wang Y, De Clercq E (April 2022). 8572: 8492: 7663: 7007: 6963:"Natural products as enzyme inhibitors." 6244: 5910: 5459: 5394: 5358:"Mechanism of Action Assays for Enzymes" 4969: 4967: 4728:Kuriyan J, Konforti B, Wemmer D (2012). 4534: 4455:Sanrattana W, Maas C, de Maat S (2019). 4258: 4110: 3859: 3726: 3718: 3687:Proteins can also be natural poisons or 3546: 3535:inhibitor of the bacterial ribonuclease 3290: 3253: 2685: 2180: 352: 31: 9521:Database of drugs and enzyme inhibitors 8757:(1st ed.). Boca Raton: CRC Press. 8400: 8265: 8178:European Journal of Medicinal Chemistry 8052: 7864:Finkel R, Cubeddu LX, Clark MA (2009). 7311: 7086:"Chapter 5: Specific Enzyme Inhibitors" 6849: 6706: 6160: 6038: 5954: 5816:Medicinal Chemistry of Anticancer Drugs 5190:Enzyme Kinetics: Principles and Methods 5151: 4893: 4825: 4686: 4394: 4350: 4303:Journal of the Royal Society, Interface 4106: 3615:, from the plant species in the family 3452: 3384:, two molecules of an inhibitor called 3319:(DFP) is an example of an irreversible 2986:Reaction of the irreversible inhibitor 2887:, a therapeutically effective class of 2804:Peptide-based HIV-1 protease inhibitor 2708: 14: 10420: 9172: 8314: 8230: 7585: 6539: 6468: 6167:An Introduction to Medicinal Chemistry 6074:Breen ME, Soellner MB (January 2015). 5916: 5034:"Physiology: Noncompetitive Inhibitor" 4881:from the original on 26 September 2009 4693:An Introduction to Medicinal Chemistry 3842:cGMP specific phosphodiesterase type 5 3064:groups; these include the amino acids 10130: 9976: 9541: 9108: 8777: 8752: 8495:Current Topics in Medicinal Chemistry 7349:Natural Products as Enzyme Inhibitors 7260: 6874: 6311:Price N, Hames B, Rickwood D (1996). 6041:Current Protein & Peptide Science 5340: 5237: 5052:from the original on 28 November 2021 4973: 4964: 4950:(4th ed.). Weinheim: Wiley-VCH. 4861:Berg J, Tymoczko J, Stryer L (2002). 4776:"The Taxonomy of Covalent Inhibitors" 4296: 4119:New drugs are the products of a long 3975:, and terminase inhibitors targeting 3743:is a widely used drug that acts as a 3664:, which is found in relatives of the 3521:. Many of these are activated by the 2822:Nonpeptidic HIV-1 protease inhibitor 246: 9444:Elsässer B, Goettig P (March 2021). 9327:Satz AL, Kuai L, Peng X (May 2021). 9026: 8628:Gubareva L, Mohan T (January 2022). 7371: 7267:Bioorganic & Medicinal Chemistry 7145:from the original on 17 January 2023 7049:Dale's Pharmacology Condensed E-Book 6989:from the original on 5 December 2022 5343:Medicinal Chemistry and Drug Design. 5242:(New ed.). Wiley–Interscience. 4978:(New ed.). Wiley-Interscience. 4689:"Chapter 7: Enzymes as Drug Targets" 3927:differences in the structure of the 2949:and are less likely to be degraded. 2933:in the reaction of the viral enzyme 27:Molecule that blocks enzyme activity 9278:Ciulli A, Abell C (December 2007). 8899:Mini Reviews in Medicinal Chemistry 8172:Cochrane SA, Lohans CT (May 2020). 7967:Expert Review of Anticancer Therapy 7866:"Chapter 41: Antiinfammatory Drugs" 7045:"Venoms, toxins, poisons and herbs" 6916:The Journal of Biological Chemistry 6889:10.1146/annurev.bi.53.070184.002425 6764:The Journal of Biological Chemistry 6713:The Journal of Biological Chemistry 6555:The Journal of Biological Chemistry 98:most difficult step of the reaction 24: 9506:from the original on 1 April 2022. 8975:Hirai K, Uchida A, Ohno R (2012). 8461:10.1016/B978-0-12-814515-9.00126-0 8212:from the original on 28 March 2023 7886:from the original on 28 March 2023 7293:from the original on 28 March 2023 7106:from the original on 28 March 2023 7065:from the original on 25 April 2013 6685:10.1111/j.1432-1033.1971.tb01215.x 6183:from the original on 28 March 2023 5215:Enzyme Kinetics: A Modern Approach 5156:. Benjamin/Cummings. p. 437. 4609:from the original on 28 March 2023 4434:. Hoboken: John Wiley & Sons. 4373:from the original on 28 March 2023 3890:made of a net-like polymer called 3655:muscarinic acetylcholine receptors 3542: 3378:from the human protozoan parasite 2862:) with cellular cofactors such as 2567: 2530: 2414: 2363: 2324: 1661: 539: 25: 10454: 9492: 9415:10.2174/1381612824999201105164942 9033:Environmental Health Perspectives 9005:from the original on 27 June 2022 8911:10.2174/1389557517666170120153930 8878:from the original on 30 June 2022 8800:from the original on 21 July 2022 8538:Expert Opinion on Pharmacotherapy 8507:10.2174/1568026619666190619115243 8339:from the original on 9 April 2022 8137:European Journal of Endocrinology 6491:from the original on 20 July 2022 5376:from the original on 15 June 2022 4709:from the original on 20 July 2022 4353:"Principles of Metabolic Control" 3591:and inhibits their assembly into 3164:Irreversible inhibition mechanism 2864:nicotinamide adenine dinucleotide 9437: 9369: 9284:Current Opinion in Biotechnology 9236: 9201: 9166: 9151: 9077: 9020: 8981:Herbicide Classes in Development 8968: 8861: 8821:"Treatment of Myasthenia Gravis" 8746: 8721: 8443: 8401:Yao J, Rock CO (November 2017). 8308: 8124: 6672:European Journal of Biochemistry 4750:from the original on 7 June 2022 4457:"SERPINs-From Trap to Treatment" 4200: 4075:, other herbicides, such as the 3965:reverse-transcriptase inhibitors 3286: 3185:called the inactivation rate or 3170: 2998: 2979: 2908: 2815: 2797: 2783: 2721:regulatory feature in metabolism 2680: 2229:isothermal titration calorimetry 2038:term proposed above to modulate 502: 378: 366: 132:is an important way to maintain 9519:. National Library of Medicine. 8699:10.1016/j.antiviral.2018.11.005 8046: 7819: 7684: 7666:Veterinary and Human Toxicology 7657: 7622: 7579: 7536: 7425: 7390: 7365: 7340: 7305: 7254: 7229: 7186: 7118: 7077: 7036: 6954: 6903: 6843: 6802: 6700: 6659: 6624: 6583: 6462: 6370: 6329: 6304: 6263: 6238: 6116: 6032: 5832: 5702: 5659: 5632: 5597: 5562: 5521: 5496: 5415: 5388: 5231: 5145: 4948:Fundamentals of Enzyme Kinetics 4854: 4721: 4035:, are used in the treatment of 3915:R61 (the protein is shown as a 3633:acetylcholinesterase inhibitors 3395: 3249: 309:that contain an autoinhibitory 9378:Drug Discovery and Development 7914:Nature Reviews. Drug Discovery 7701:10.1016/B0-12-227055-X/00934-2 7314:Trends in Biochemical Sciences 6315:. BIOS Scientific Publishers. 6204:Journal of Medicinal Chemistry 5606:Journal of Medicinal Chemistry 5462:Journal of Theoretical Biology 5424:Trends in Biochemical Sciences 4499: 4161:DNA Encoded Chemical Libraries 3931:in bacteria, or how they make 3855: 3846:cyclic guanosine monophosphate 3563:that interfere with digestion. 3437:, an enzyme which breaks down 2553: 2547: 2491: 2485: 2441: 2435: 2419: 2398: 2393: 2387: 2368: 2347: 2335: 2329: 2298: 2292: 2142: 2134: 2121: 2115: 2103: 2071: 1981: 1973: 1960: 1954: 1942: 1910: 1841: 1833: 1820: 1814: 1802: 1770: 1710: 1702: 1689: 1683: 1596: 1588: 1575: 1569: 1516: 1508: 1495: 1489: 1424: 1416: 1390: 1384: 1328: 1320: 1295: 1287: 1245: 1237: 1212: 1204: 1149: 1141: 1135: 1127: 1107: 1099: 1074: 1066: 1060: 1052: 937: 929: 833: 827: 616:of the enzyme. In the classic 453: 427:covalent reversible inhibitors 360:Inhibition mechanism schematic 40:(E) accelerates conversion of 13: 1: 9403:Current Pharmaceutical Design 9175:Current Pharmaceutical Design 8874:(5th ed.). McGraw Hill. 8550:10.1080/14656566.2018.1454428 8055:Current Pharmaceutical Design 8024:10.1016/S0140-6736(21)00438-4 7979:10.1080/14737140.2018.1527688 7608:10.1016/S0041-0101(97)00074-3 7545:The Annals of Pharmacotherapy 7016:(4). New York, N.Y.: 209–28. 6877:Annual Review of Biochemistry 6823:10.1016/S0076-6879(67)11085-9 6726:10.1016/S0021-9258(19)47263-3 6568:10.1016/S0021-9258(18)48472-4 6355:10.1016/S1074-5521(00)90060-7 6284:10.1016/S0921-0423(98)80013-0 5841:Current Pharmaceutical Design 5653:10.1016/S0040-4020(01)81773-7 5482:10.1016/S0022-5193(05)80481-3 5403:(1): 164–6, 168, 170 passim. 4867:. W. H. Freeman and Company. 4774:Tuley A, Fast W (June 2018). 4555:10.1080/10409238.2020.1742090 4409:10.1016/s1359-6446(03)02713-2 4238: 4157:fragment-based lead discovery 4062: 3982: 3938: 3242:. This will produce a set of 3153:is the rate of inactivation. 2730: 301:in one of the tightest known 9296:10.1016/j.copbio.2007.09.003 9257:10.1016/j.drudis.2006.04.005 9128:10.1016/j.drudis.2021.01.006 9111:"Drug discovery for enzymes" 8989:10.1007/978-3-642-59416-8_10 8728:Kuhr RJ, Dorough HW (1976). 8419:10.1016/j.bbalip.2016.09.014 8190:10.1016/j.ejmech.2020.112262 7840:10.1016/j.bbapap.2004.06.004 7326:10.1016/0968-0004(89)90104-7 7236:Price NC, Stevens L (1999). 7043:Page C, Pitchford S (2021). 6707:Reardon JE (November 1989). 6645:10.1016/0167-4838(86)90067-1 6600:10.1016/0076-6879(95)49034-5 6216:10.1021/acs.jmedchem.8b01153 6137:10.1016/j.bbapap.2005.07.025 5955:Schramm VL (November 2018). 5818:. Elsevier. pp. 54–58. 5538:10.1016/0076-6879(95)49039-6 5436:10.1016/0968-0004(90)90295-M 5320:10.1016/j.bbagen.2007.01.001 4840:10.1016/0926-6569(63)90226-8 4655:10.1371/journal.pone.0214255 4126:The first general method is 3825:biosynthesis. This block of 3602:Many natural poisons act as 3495:phosphofructokinase‑1 3279:, and the activated form of 3156: 2847:N-10-formyl tetrahydrofolate 303:protein–protein interactions 7: 10156: 8646:10.1101/cshperspect.a038455 8585:Acta Pharmaceutica Sinica B 8266:Dalhoff A (February 2021). 7631:Current Medicinal Chemistry 7434:Current Cancer Drug Targets 6249:(3rd ed.). CRC Press. 6006:Current Medicinal Chemistry 5973:10.1021/acs.chemrev.8b00369 5919:Current Medicinal Chemistry 5688:10.1126/science.279.5347.98 5571:Annals of Internal Medicine 5009:10.1533/9780857099921.2.126 4792:10.1021/acs.biochem.8b00315 4193: 4188:structure-based drug design 4184:crystallographic structures 3784:Inhibitors of Janus kinases 3473:is a classic example. This 3232:peptide mass fingerprinting 2873: 10: 10459: 9738:Dihydropteroate synthetase 9597:Non-competitive inhibition 9346:10.1016/j.bmcl.2021.127851 9187:10.2174/138161206777585201 8597:10.1016/j.apsb.2021.11.009 8360:Medicinal Research Reviews 8315:Mobley H (13 March 2006). 8284:10.1007/s15010-020-01536-y 8102:10.1016/j.sxmr.2018.06.005 7481:10.2174/138527206776894410 7411:10.2174/138945006776054942 6428:Medicinal Research Reviews 6377:Maurer T, Fung HL (2000). 5931:10.2174/092986711797287566 5876:Medicinal Research Reviews 5853:10.2174/138161206776361110 4297:Sauro HM (February 2017). 4141:transition state analogues 3317:Diisopropylfluorophosphate 3200:. Fitting these data to a 2988:diisopropylfluorophosphate 546:non-competitive inhibition 496: 10313: 10305:Michaelis–Menten kinetics 10277: 10246: 10215: 10164: 10011: 9958:Steroidogenesis inhibitor 9950: 9922: 9798: 9705: 9622: 9615: 9579: 8946:10.1007/s00726-005-0254-1 8837:10.1016/j.ncl.2018.01.011 8753:Stone TW (October 2020). 7469:Current Organic Chemistry 7279:10.1016/j.bmc.2004.05.041 6272:Progress in Biotechnology 6163:"Enzymes as Drug Targets" 5782:10.3109/14756360902843809 5583:10.7326/0003-4819-86-1-65 4946:Cornish-Bowden A (2012). 4269:10.1002/9781118540398.ch1 4232:Transition state analogue 4216:Activity-based proteomics 4148:high-throughput screening 4101:oxidative phosphorylation 3764:receptor tyrosine kinases 3504:fructose 2,6-bisphosphate 3351:α-difluoromethylornithine 3118:/ values are used, where 2775:Multi-substrate analogues 2255:Michaelis–Menten equation 400:non-covalent interactions 10197:Diffusion-limited enzyme 9894:Matrix metalloproteinase 9697:Ribonucleotide reductase 9592:Uncompetitive inhibition 8732:. Cleveland: CRC Press. 8452:Encyclopedia of Virology 8067:10.2174/1381612033453712 7920:(1): 19–34 (Figure 1C). 7643:10.2174/0929867023368827 7446:10.2174/1568009033481967 7261:Smyth TP (August 2004). 6525:10.1016/j.ab.2012.08.006 6053:10.2174/1389203033487054 6018:10.2174/0929867003374886 5118:10.1177/2472555219829898 4019:, are absorbed from the 3969:neuraminidase inhibitors 3786:block the production of 3714: 3643:from deadly nightshade ( 3012:Irreversible inhibitors 2965: 2909:"competitive inhibition" 2737:conformational isomerism 2639:Lineweaver–Burk diagrams 604:Quantitative description 570: 527:Le Chatelier's principle 509:uncompetitive inhibition 408:hydrophobic interactions 333:inhibitors are known as 10071:Lipinski's rule of five 9663:Dihydrofolate reductase 9109:Rufer AC (April 2021). 8090:Sexual Medicine Reviews 7351:. Singapore: Springer. 7207:10.1002/biof.5520100101 6513:Analytical Biochemistry 6342:Chemistry & Biology 5736:10.1073/pnas.0909141107 4474:10.3389/fmed.2019.00025 4130:based on mimicking the 3999:into its constituents, 3991:are enzyme inhibitors. 3832:A common treatment for 3819:dihydrofolate reductase 3573:small organic molecules 3376:trypanothione reductase 3363:Ornithine decarboxylase 3359:African trypanosomiasis 3357:, and is used to treat 3296:Trypanothione reductase 2961:Irreversible inhibitors 2881:dihydrofolate reductase 2769:irreversible inhibition 295:ribonuclease inhibitors 9759:Nucleotidyltransferase 9587:Competitive inhibition 7794:10.3390/toxins11060350 7743:10.3390/toxins11060324 7347:Maheshwari VL (2022). 6929:10.1074/jbc.M403187200 6777:10.1074/jbc.M403187200 5345:(16). InTech: 357–372. 4355:. In Storey KB (ed.). 4315:10.1098/rsif.2016.0848 4172:Computer-based methods 4116: 3945:replication of viruses 3883: 3788:inflammatory cytokines 3736: 3724: 3670:RNA polymerase II 3651:competitive antagonist 3649:) that functions as a 3564: 3329:acetylcholine esterase 3313: 3263: 2868:adenosine triphosphate 2581: 2511: 2451: 2186: 2177:Dissociation constants 2167: 2006: 1866: 1735: 1621: 1541: 1458: 623:dissociation constants 460:competitive inhibition 233:adverse drug reactions 221:dissociation constants 49: 10428:Biochemical reactions 10290:Eadie–Hofstee diagram 10223:Allosteric regulation 10076:Lipophilic efficiency 9769:Reverse transcriptase 9027:Duke SO (July 1990). 8782:. In Gupta RC (ed.). 8150:10.1530/eje.0.1430143 5362:Assay Guidance Manual 5188:Bisswanger H (2017). 4906:"Types of Inhibition" 4587:Rydzewski RM (2010). 4461:Frontiers in Medicine 4114: 4095:and the processes of 4081:acetolactate synthase 3977:human cytomegalovirus 3863: 3792:inflammatory diseases 3730: 3722: 3569:secondary metabolites 3550: 3361:(sleeping sickness). 3294: 3269:conformational change 3257: 2723:and can be a form of 2686:Partially competitive 2582: 2512: 2452: 2191:dissociation constant 2184: 2168: 2007: 1867: 1736: 1622: 1542: 1459: 1437:multiply out by 353:Reversible inhibitors 329:of the enzyme. These 272:secondary metabolites 35: 10300:Lineweaver–Burk plot 9815:Acetylcholinesterase 9722:Thymidylate synthase 9463:10.3390/ijms22063232 9245:Drug Discovery Today 9115:Drug Discovery Today 8233:ACS Chemical Biology 7926:10.1038/nrd.2016.230 7399:Current Drug Targets 7376:. Berlin: Springer. 7084:Stenersen J (2004). 6839:on 28 February 2018. 6245:Lundblad RL (2004). 6080:ACS Chemical Biology 5647:(14–15): 2351–2364. 5111:(5): 515–522 (516). 4397:Drug Discovery Today 4128:rational drug design 4107:Discovery and design 3993:Acetylcholinesterase 3967:targeting HIV/AIDS, 3834:erectile dysfunction 3678:protein phosphatases 3453:Metabolic regulation 3435:acetylcholinesterase 2889:antiretroviral drugs 2870:(ATP) respectively. 2709:Substrate or product 2698:, but an unaffected 2522: 2467: 2264: 2251:nonlinear regression 2052: 1891: 1751: 1645: 1557: 1477: 778: 425:. A special case is 10433:Medicinal chemistry 10091:New chemical entity 10081:Mechanism of action 10005:medicinal chemistry 9909:Histone deacetylase 9743:Farnesyltransferase 8321:Scientific American 7600:1998Txcn...36...13V 6922:(28): 29493–29500. 6850:Brenner GM (2000). 6719:(32): 19039–19044. 6278:. Elsevier: 77–82. 6161:Patrick GL (2017). 5967:(22): 11194–11258. 5727:2010PNAS..107.4878A 5680:1998Sci...279...98R 5618:10.1021/jm00125a002 5474:1990JThBi.145..457T 5268:Integrative Biology 5152:Laidler KJ (1978). 4912:on 8 September 2011 4687:Patrick GL (2013). 4646:2019PLoSO..1414255J 4520:10.1021/bi00222a030 4351:Plaxton WC (2004). 4180:molecular mechanics 4079:inhibit the enzyme 4071:is an inhibitor of 4047:pesticides such as 3953:protease inhibitors 3707:. This enzyme is a 3584:, binds tightly to 3100:will hydrolyse the 2895:. The structure of 2885:protease inhibitors 2839:purine biosynthesis 2571: 2131: 2111: 1970: 1950: 1830: 1810: 1699: 1679: 1585: 1565: 1505: 1485: 1400: 1380: 1304: 1271: 1221: 1201: 1083: 1036: 981: 962: 913: 894: 843: 823: 809: 790: 488:point, or half the 264:primary metabolites 217:genetically distant 193:protease inhibitors 189:rheumatic arthritis 179:. Examples include 84:are converted into 82:substrate molecules 10259:Enzyme superfamily 10192:Enzyme promiscuity 9942:Carbonic anhydrase 9934:Dopa decarboxylase 9602:Suicide inhibition 9251:(11–12): 561–568. 8825:Neurologic Clinics 8687:Antiviral Research 8018:(10302): 803–816. 6469:Purich DL (2010). 5280:10.1039/c1ib00053e 4117: 3911:from the bacteria 3884: 3737: 3725: 3693:trypsin inhibitors 3565: 3561:trypsin inhibitors 3471:glycolytic pathway 3461:control in cells. 3441:, and are used as 3386:quinacrine mustard 3343:Suicide inhibition 3321:protease inhibitor 3314: 3264: 3068:(that reacts with 3042:fluorophosphonates 2907:, as shown in the 2577: 2557: 2507: 2447: 2187: 2163: 2159: 2126: 2002: 1998: 1965: 1862: 1858: 1825: 1731: 1727: 1694: 1617: 1613: 1580: 1537: 1533: 1500: 1454: 1452: 1428: 1395: 1332: 1299: 1249: 1216: 1160: to numerator 1111: 1078: 995: 976: 941: 908: 862: 857: 838: 804: 594:tertiary structure 255:to macromolecular 247:Structural classes 74:chemical reactions 50: 10443:Enzyme inhibitors 10415: 10414: 10124: 10123: 10066:Ligand efficiency 9970: 9969: 9966: 9965: 9838:Alpha-glucosidase 9828:Polygalacturonase 9810:Phosphodiesterase 9751:GABA transaminase 9655:Monoamine oxidase 9639:HMG-CoA reductase 9573:enzyme inhibition 9409:(44): 5684–5699. 9387:978-1-315-11347-0 9216:(15): 2644–2676. 9210:Angewandte Chemie 9181:(17): 2087–2097. 9095:978-1-00-043721-8 8998:978-3-642-59416-8 8905:(17): 1665–1676. 8793:978-0-08-054310-9 8778:Gupta RC (2006). 8764:978-1-00-009898-3 8739:978-0-87819-052-2 8501:(18): 1571–1598. 8471:978-0-12-814516-6 8413:(11): 1300–1309. 8372:10.1002/med.21780 8245:10.1021/cb700182u 8061:(31): 2593–2613. 7973:(12): 1249–1270. 7879:978-0-7817-7155-9 7710:978-0-12-227055-0 7637:(22): 1981–1989. 7557:10.1345/aph.1D536 7513:10.1159/000486546 7383:978-3-540-00118-8 7358:978-981-19-0932-0 7273:(15): 4081–4088. 7247:978-0-19-850229-6 7179:978-3-642-13865-2 7099:978-0-203-64683-0 7058:978-0-7020-7819-4 7022:10.1002/tcr.20045 6979:978-3-527-34205-1 6861:978-0-7216-7757-6 6832:978-0-12-181860-9 6770:(28): 29493–500. 6609:978-0-12-182150-0 6484:978-0-12-380925-4 6322:978-0-12-564710-6 6293:978-0-444-82970-2 6256:978-0-8493-1983-9 6210:(12): 5673–5724. 6176:978-0-19-874969-1 6092:10.1021/cb5008376 5888:10.1002/med.21475 5847:(11): 1301–1314. 5825:978-0-444-62667-7 5721:(11): 4878–4883. 5514:978-0-470-20745-1 5274:(12): 1197–1201. 5249:978-0-471-30309-1 5238:Segel IH (1993). 5224:978-0-471-15985-8 5199:978-3-527-80647-8 5163:978-0-8053-5680-9 5085:978-1-118-91840-1 5018:978-1-904275-27-5 4985:978-0-471-30309-1 4974:Segel IH (1993). 4957:978-3-527-66549-5 4874:978-0-7167-4955-4 4786:(24): 3326–3337. 4743:978-1-135-08892-7 4702:978-0-19-969739-7 4602:978-0-08-091488-6 4441:978-3-527-65970-8 4366:978-0-471-67557-0 4278:978-1-118-48813-3 4176:molecular docking 4152:virtual screening 4037:myasthenia gravis 3850:corpus cavernosum 3772:kinase inhibitors 3745:suicide inhibitor 3731:The structure of 3646:Atropa belladonna 3528:trypsin inhibitor 3499:negative feedback 3477:pathway consumes 3459:metabolic pathway 3381:Trypanosoma cruzi 3224:mass spectrometry 3198:exponential decay 3098:hydrochloric acid 3090:protein structure 3038:phenyl sulfonates 3034:Michael acceptors 3018:nitrogen mustards 2725:negative feedback 2635:Hanes-Woolf plots 2572: 2505: 2445: 2339: 2161: 2140: 2130: 2120: 2110: 2000: 1979: 1969: 1959: 1949: 1860: 1839: 1829: 1819: 1809: 1729: 1708: 1698: 1688: 1678: 1615: 1594: 1584: 1574: 1564: 1535: 1514: 1504: 1494: 1484: 1438: 1430: 1422: 1399: 1389: 1379: 1334: 1326: 1303: 1293: 1270: 1264: 1251: 1243: 1220: 1210: 1200: 1161: 1147: 1133: 1125: 1113: 1105: 1082: 1072: 1058: 1035: 997: 980: 961: 955: 954:multiply by 943: 935: 912: 893: 864: 859: 842: 832: 822: 808: 789: 638:', respectively. 614:kinetic constants 130:negative feedback 126:metabolic pathway 60:that binds to an 18:Enzyme inhibition 16:(Redirected from 10450: 10295:Hanes–Woolf plot 10238:Enzyme activator 10233:Enzyme inhibitor 10207:Enzyme catalysis 10151: 10144: 10137: 10128: 10127: 10101:Pharmacokinetics 10096:Pharmacodynamics 10061:Enzyme inhibitor 10046:Drug development 9997: 9990: 9983: 9974: 9973: 9692:Xanthine oxidase 9634:Aldose reductase 9620: 9619: 9607:Mixed inhibition 9562: 9555: 9548: 9539: 9538: 9533: 9532:on 20 June 2006. 9528:. Archived from 9520: 9507: 9486: 9485: 9475: 9465: 9441: 9435: 9434: 9398: 9392: 9391: 9373: 9367: 9366: 9348: 9324: 9318: 9317: 9307: 9275: 9269: 9268: 9240: 9234: 9233: 9205: 9199: 9198: 9170: 9164: 9163: 9155: 9149: 9148: 9130: 9106: 9100: 9099: 9081: 9075: 9074: 9064: 9024: 9018: 9017: 9012: 9010: 8972: 8966: 8965: 8929: 8923: 8922: 8894: 8888: 8887: 8885: 8883: 8865: 8859: 8858: 8848: 8816: 8810: 8809: 8807: 8805: 8775: 8769: 8768: 8750: 8744: 8743: 8725: 8719: 8718: 8682: 8676: 8675: 8657: 8625: 8619: 8618: 8608: 8591:(4): 1567–1590. 8576: 8570: 8569: 8533: 8527: 8526: 8490: 8484: 8483: 8463: 8447: 8441: 8440: 8430: 8398: 8392: 8391: 8366:(4): 1855–1889. 8355: 8349: 8348: 8346: 8344: 8312: 8306: 8305: 8295: 8263: 8257: 8256: 8228: 8222: 8221: 8219: 8217: 8169: 8163: 8162: 8152: 8128: 8122: 8121: 8085: 8079: 8078: 8050: 8044: 8043: 8007: 8001: 8000: 7990: 7958: 7952: 7951: 7937: 7905: 7896: 7895: 7893: 7891: 7861: 7852: 7851: 7823: 7817: 7816: 7806: 7796: 7772: 7766: 7765: 7755: 7745: 7721: 7715: 7714: 7688: 7682: 7681: 7661: 7655: 7654: 7626: 7620: 7619: 7583: 7577: 7576: 7540: 7534: 7533: 7515: 7506:(3–4): 131–151. 7491: 7485: 7484: 7464: 7458: 7457: 7429: 7423: 7422: 7394: 7388: 7387: 7369: 7363: 7362: 7344: 7338: 7337: 7309: 7303: 7302: 7300: 7298: 7258: 7252: 7251: 7233: 7227: 7226: 7190: 7184: 7183: 7161: 7155: 7154: 7152: 7150: 7122: 7116: 7115: 7113: 7111: 7081: 7075: 7074: 7072: 7070: 7040: 7034: 7033: 7005: 6999: 6998: 6996: 6994: 6988: 6967: 6958: 6952: 6951: 6941: 6931: 6907: 6901: 6900: 6872: 6866: 6865: 6847: 6841: 6840: 6835:. Archived from 6815:Enzyme Structure 6806: 6800: 6799: 6789: 6779: 6755: 6745: 6739: 6738: 6728: 6704: 6698: 6697: 6687: 6663: 6657: 6656: 6628: 6622: 6621: 6587: 6581: 6580: 6570: 6546: 6537: 6536: 6507: 6501: 6500: 6498: 6496: 6466: 6460: 6459: 6423: 6417: 6416: 6406: 6395:10.1208/ps020108 6374: 6368: 6367: 6357: 6333: 6327: 6326: 6308: 6302: 6301: 6267: 6261: 6260: 6242: 6236: 6235: 6199: 6193: 6192: 6190: 6188: 6158: 6149: 6148: 6120: 6114: 6113: 6103: 6071: 6065: 6064: 6036: 6030: 6029: 6001: 5995: 5994: 5984: 5961:Chemical Reviews 5952: 5943: 5942: 5914: 5908: 5907: 5882:(4): 1295–1331. 5871: 5865: 5864: 5836: 5830: 5829: 5811: 5802: 5801: 5765: 5759: 5758: 5748: 5738: 5706: 5700: 5699: 5674:(5347): 98–102. 5663: 5657: 5656: 5636: 5630: 5629: 5601: 5595: 5594: 5566: 5560: 5559: 5525: 5519: 5518: 5500: 5494: 5493: 5457: 5448: 5447: 5419: 5413: 5412: 5392: 5386: 5385: 5383: 5381: 5353: 5347: 5346: 5338: 5332: 5331: 5303: 5292: 5291: 5263: 5254: 5253: 5235: 5229: 5228: 5210: 5204: 5203: 5185: 5168: 5167: 5149: 5143: 5142: 5120: 5096: 5090: 5089: 5071: 5062: 5061: 5059: 5057: 5029: 5023: 5022: 4996: 4990: 4989: 4971: 4962: 4961: 4943: 4922: 4921: 4919: 4917: 4902: 4891: 4890: 4888: 4886: 4858: 4852: 4851: 4823: 4814: 4813: 4803: 4771: 4760: 4759: 4757: 4755: 4725: 4719: 4718: 4716: 4714: 4684: 4678: 4677: 4667: 4657: 4625: 4619: 4618: 4616: 4614: 4584: 4575: 4574: 4538: 4532: 4531: 4514:(8): 2246–2255. 4503: 4497: 4496: 4486: 4476: 4452: 4446: 4445: 4427: 4421: 4420: 4392: 4383: 4382: 4380: 4378: 4348: 4337: 4336: 4326: 4294: 4283: 4282: 4256: 4210: 4205: 4204: 4137:functional group 4132:transition state 4121:drug development 3961:Hepatitis C 3881: 3872:transpeptidase ( 3867: 3705:castor oil beans 3582:Pacific yew tree 3447:chemical warfare 3390:nitrogen mustard 3338: 3311: 3174: 3002: 2983: 2916:transition state 2819: 2801: 2787: 2586: 2584: 2583: 2578: 2573: 2570: 2565: 2556: 2545: 2534: 2533: 2516: 2514: 2513: 2508: 2506: 2504: 2503: 2494: 2483: 2456: 2454: 2453: 2448: 2446: 2444: 2431: 2430: 2418: 2417: 2408: 2396: 2386: 2385: 2367: 2366: 2357: 2345: 2340: 2338: 2328: 2327: 2315: 2314: 2301: 2291: 2290: 2274: 2172: 2170: 2169: 2164: 2162: 2160: 2158: 2157: 2156: 2141: 2138: 2127: 2125: 2124: 2118: 2107: 2102: 2101: 2086: 2085: 2067: 2066: 2011: 2009: 2008: 2003: 2001: 1999: 1997: 1996: 1995: 1980: 1977: 1966: 1964: 1963: 1957: 1946: 1941: 1940: 1925: 1924: 1906: 1905: 1871: 1869: 1868: 1863: 1861: 1859: 1857: 1856: 1855: 1840: 1837: 1826: 1824: 1823: 1817: 1806: 1801: 1800: 1785: 1784: 1766: 1765: 1740: 1738: 1737: 1732: 1730: 1728: 1726: 1725: 1724: 1709: 1706: 1695: 1693: 1692: 1686: 1675: 1673: 1672: 1657: 1656: 1626: 1624: 1623: 1618: 1616: 1614: 1612: 1611: 1610: 1595: 1592: 1581: 1579: 1578: 1572: 1561: 1546: 1544: 1543: 1538: 1536: 1534: 1532: 1531: 1530: 1515: 1512: 1501: 1499: 1498: 1492: 1481: 1463: 1461: 1460: 1455: 1453: 1449: 1448: 1439: 1436: 1433: 1431: 1429: 1427: 1423: 1420: 1412: 1411: 1396: 1394: 1393: 1387: 1376: 1374: 1373: 1361: 1360: 1345: 1335: 1333: 1331: 1327: 1324: 1316: 1315: 1300: 1298: 1294: 1291: 1283: 1282: 1267: 1265: 1262: 1259: 1257: 1253: 1252: 1250: 1248: 1244: 1241: 1233: 1232: 1217: 1215: 1211: 1208: 1197: 1184: 1183: 1182: 1166: 1162: 1159: 1148: 1145: 1134: 1131: 1126: 1123: 1120: 1118: 1114: 1112: 1110: 1106: 1103: 1095: 1094: 1079: 1077: 1073: 1070: 1059: 1056: 1048: 1047: 1032: 1026: 1025: 1024: 1008: 998: 996: 994: 993: 992: 977: 975: 974: 973: 958: 956: 953: 950: 948: 944: 942: 940: 936: 933: 925: 924: 909: 907: 906: 905: 890: 884: 883: 882: 865: 863: 861: 860: 858: 856: 855: 854: 839: 837: 836: 830: 819: 805: 803: 802: 801: 786: 618:Michaelis-Menten 577:mixed inhibition 382: 370: 315:intramolecularly 297:, which bind to 187:and in treating 54:enzyme inhibitor 21: 10458: 10457: 10453: 10452: 10451: 10449: 10448: 10447: 10418: 10417: 10416: 10411: 10323:Oxidoreductases 10309: 10285:Enzyme kinetics 10273: 10269:List of enzymes 10242: 10211: 10182:Catalytic triad 10160: 10155: 10125: 10120: 10021:Bioavailability 10007: 10001: 9971: 9962: 9946: 9918: 9794: 9781:Tyrosine kinase 9701: 9611: 9575: 9566: 9524: 9511: 9498: 9495: 9490: 9489: 9442: 9438: 9399: 9395: 9388: 9374: 9370: 9325: 9321: 9276: 9272: 9241: 9237: 9206: 9202: 9171: 9167: 9156: 9152: 9107: 9103: 9096: 9082: 9078: 9045:10.2307/3431034 9025: 9021: 9008: 9006: 8999: 8973: 8969: 8930: 8926: 8895: 8891: 8881: 8879: 8866: 8862: 8817: 8813: 8803: 8801: 8794: 8776: 8772: 8765: 8751: 8747: 8740: 8726: 8722: 8683: 8679: 8626: 8622: 8577: 8573: 8534: 8530: 8491: 8487: 8472: 8448: 8444: 8399: 8395: 8356: 8352: 8342: 8340: 8313: 8309: 8264: 8260: 8229: 8225: 8215: 8213: 8170: 8166: 8129: 8125: 8086: 8082: 8051: 8047: 8008: 8004: 7959: 7955: 7906: 7899: 7889: 7887: 7880: 7862: 7855: 7824: 7820: 7773: 7769: 7722: 7718: 7711: 7689: 7685: 7662: 7658: 7627: 7623: 7584: 7580: 7541: 7537: 7492: 7488: 7465: 7461: 7430: 7426: 7395: 7391: 7384: 7372:Birk Y (2003). 7370: 7366: 7359: 7345: 7341: 7320:(11): 450–454. 7310: 7306: 7296: 7294: 7259: 7255: 7248: 7234: 7230: 7191: 7187: 7180: 7162: 7158: 7148: 7146: 7123: 7119: 7109: 7107: 7100: 7082: 7078: 7068: 7066: 7059: 7041: 7037: 7010:Chemical Record 7006: 7002: 6992: 6990: 6986: 6980: 6965: 6959: 6955: 6908: 6904: 6873: 6869: 6862: 6848: 6844: 6833: 6807: 6803: 6747: 6746: 6742: 6705: 6701: 6664: 6660: 6629: 6625: 6610: 6588: 6584: 6547: 6540: 6508: 6504: 6494: 6492: 6485: 6467: 6463: 6424: 6420: 6375: 6371: 6334: 6330: 6323: 6313:Proteins LabFax 6309: 6305: 6294: 6268: 6264: 6257: 6243: 6239: 6200: 6196: 6186: 6184: 6177: 6159: 6152: 6121: 6117: 6072: 6068: 6037: 6033: 6002: 5998: 5953: 5946: 5925:(29): 4513–37. 5915: 5911: 5872: 5868: 5837: 5833: 5826: 5812: 5805: 5776:(6): 1291–318. 5766: 5762: 5707: 5703: 5664: 5660: 5637: 5633: 5602: 5598: 5567: 5563: 5548: 5526: 5522: 5515: 5501: 5497: 5458: 5451: 5430:(12): 455–458. 5420: 5416: 5393: 5389: 5379: 5377: 5354: 5350: 5339: 5335: 5304: 5295: 5264: 5257: 5250: 5236: 5232: 5225: 5211: 5207: 5200: 5186: 5171: 5164: 5150: 5146: 5097: 5093: 5086: 5072: 5065: 5055: 5053: 5030: 5026: 5019: 4997: 4993: 4986: 4972: 4965: 4958: 4944: 4925: 4915: 4913: 4904: 4903: 4894: 4884: 4882: 4875: 4859: 4855: 4824: 4817: 4772: 4763: 4753: 4751: 4744: 4726: 4722: 4712: 4710: 4703: 4685: 4681: 4640:(3): e0214255. 4626: 4622: 4612: 4610: 4603: 4585: 4578: 4539: 4535: 4504: 4500: 4453: 4449: 4442: 4428: 4424: 4393: 4386: 4376: 4374: 4367: 4349: 4340: 4295: 4286: 4279: 4257: 4246: 4241: 4206: 4199: 4196: 4109: 4065: 4045:organophosphate 3985: 3949:Antiviral drugs 3941: 3873: 3865: 3858: 3804:Crohn's disease 3717: 3606:that can cause 3545: 3543:Natural poisons 3455: 3398: 3336: 3303: 3289: 3252: 3218: 3211: 3191: 3182: 3181: 3180: 3179: 3178: 3175: 3166: 3165: 3159: 3152: 3145: 3138: 3131: 3124: 3117: 3110: 3010: 3009: 3008: 3007: 3006: 3003: 2995: 2994: 2992:serine protease 2984: 2975: 2974: 2968: 2963: 2924: 2876: 2835:formyl transfer 2830: 2829: 2828: 2827: 2826: 2820: 2811: 2810: 2809: 2802: 2793: 2792: 2791: 2788: 2777: 2766: 2759: 2752: 2745: 2733: 2711: 2704: 2697: 2688: 2683: 2676: 2669: 2662: 2651: 2627:Lineweaver–Burk 2617: 2610: 2603: 2596: 2566: 2561: 2546: 2544: 2529: 2525: 2523: 2520: 2519: 2499: 2495: 2484: 2482: 2468: 2465: 2464: 2426: 2422: 2413: 2409: 2404: 2397: 2375: 2371: 2362: 2358: 2353: 2346: 2344: 2323: 2319: 2310: 2306: 2302: 2280: 2276: 2275: 2273: 2265: 2262: 2261: 2247:enzyme activity 2244: 2237: 2226: 2219: 2212: 2205: 2198: 2179: 2152: 2148: 2137: 2133: 2128: 2114: 2113: 2108: 2106: 2094: 2090: 2078: 2074: 2059: 2055: 2053: 2050: 2049: 2044: 2037: 2029: 2022: 1991: 1987: 1976: 1972: 1967: 1953: 1952: 1947: 1945: 1933: 1929: 1917: 1913: 1898: 1894: 1892: 1889: 1888: 1882: 1851: 1847: 1836: 1832: 1827: 1813: 1812: 1807: 1805: 1793: 1789: 1777: 1773: 1758: 1754: 1752: 1749: 1748: 1720: 1716: 1705: 1701: 1696: 1682: 1681: 1676: 1674: 1668: 1664: 1652: 1648: 1646: 1643: 1642: 1637: 1606: 1602: 1591: 1587: 1582: 1568: 1567: 1562: 1560: 1558: 1555: 1554: 1526: 1522: 1511: 1507: 1502: 1488: 1487: 1482: 1480: 1478: 1475: 1474: 1451: 1450: 1444: 1440: 1435: 1432: 1419: 1407: 1403: 1402: 1397: 1383: 1382: 1377: 1375: 1369: 1365: 1356: 1352: 1343: 1342: 1323: 1311: 1307: 1306: 1301: 1290: 1278: 1274: 1273: 1268: 1266: 1261: 1258: 1240: 1228: 1224: 1223: 1218: 1207: 1203: 1198: 1196: 1189: 1185: 1178: 1174: 1173: 1164: 1163: 1158: 1144: 1130: 1122: 1119: 1102: 1090: 1086: 1085: 1080: 1069: 1055: 1043: 1039: 1038: 1033: 1031: 1027: 1020: 1016: 1015: 1006: 1005: 988: 984: 983: 978: 969: 965: 964: 959: 957: 952: 949: 932: 920: 916: 915: 910: 901: 897: 896: 891: 889: 885: 878: 874: 873: 866: 850: 846: 845: 840: 826: 825: 820: 818: 811: 806: 797: 793: 792: 787: 785: 781: 779: 776: 775: 770: 763: 748: 741: 734: 727: 717: 710: 703: 696: 686: 679: 672: 665: 655: 648: 637: 630: 606: 586:allosteric site 573: 565: 558: 542: 540:Non-competitive 534: 523: 516: 505: 497:"Drugs" section 493: 486: 479: 472: 456: 448: 441: 396: 395: 394: 393: 388: 387: 386: 383: 375: 374: 371: 362: 361: 355: 253:small molecules 249: 64:and blocks its 28: 23: 22: 15: 12: 11: 5: 10456: 10446: 10445: 10440: 10435: 10430: 10413: 10412: 10410: 10409: 10396: 10383: 10370: 10357: 10344: 10331: 10317: 10315: 10311: 10310: 10308: 10307: 10302: 10297: 10292: 10287: 10281: 10279: 10275: 10274: 10272: 10271: 10266: 10261: 10256: 10250: 10248: 10247:Classification 10244: 10243: 10241: 10240: 10235: 10230: 10225: 10219: 10217: 10213: 10212: 10210: 10209: 10204: 10199: 10194: 10189: 10184: 10179: 10174: 10168: 10166: 10162: 10161: 10154: 10153: 10146: 10139: 10131: 10122: 10121: 10119: 10118: 10113: 10108: 10103: 10098: 10093: 10088: 10086:Mode of action 10083: 10078: 10073: 10068: 10063: 10058: 10056:Drug targeting 10053: 10051:Drug discovery 10048: 10043: 10038: 10033: 10028: 10023: 10018: 10012: 10009: 10008: 10000: 9999: 9992: 9985: 9977: 9968: 9967: 9964: 9963: 9961: 9960: 9954: 9952: 9948: 9947: 9945: 9944: 9937: 9936: 9929: 9927: 9920: 9919: 9917: 9916: 9914:Beta-lactamase 9911: 9904: 9903: 9902: 9901: 9896: 9891: 9881: 9880: 9879: 9874: 9864: 9863: 9862: 9857: 9841: 9840: 9835: 9830: 9823: 9822: 9817: 9812: 9805: 9803: 9796: 9795: 9793: 9792: 9791: 9790: 9789: 9788: 9776:Protein kinase 9773: 9772: 9771: 9766: 9754: 9753: 9746: 9745: 9740: 9733: 9732: 9725: 9724: 9719: 9712: 9710: 9703: 9702: 9700: 9699: 9694: 9687: 9686: 9681: 9674: 9673: 9666: 9665: 9658: 9657: 9650: 9649: 9642: 9641: 9636: 9629: 9627: 9624:Oxidoreductase 9617: 9613: 9612: 9610: 9609: 9604: 9599: 9594: 9589: 9583: 9581: 9577: 9576: 9565: 9564: 9557: 9550: 9542: 9536: 9535: 9522: 9509: 9494: 9493:External links 9491: 9488: 9487: 9436: 9393: 9386: 9368: 9319: 9270: 9235: 9200: 9165: 9150: 9121:(4): 875–886. 9101: 9094: 9076: 9019: 8997: 8967: 8940:(2): 195–204. 8924: 8889: 8860: 8831:(2): 311–337. 8811: 8792: 8770: 8763: 8745: 8738: 8720: 8677: 8640:(1): a038455. 8620: 8571: 8544:(6): 577–587. 8528: 8485: 8470: 8442: 8393: 8350: 8307: 8258: 8223: 8164: 8143:(2): 143–154. 8123: 8096:(1): 115–128. 8080: 8045: 8002: 7953: 7897: 7878: 7853: 7818: 7767: 7716: 7709: 7683: 7672:(5): 294–297. 7656: 7621: 7578: 7551:(1): 173–176. 7535: 7486: 7475:(8): 825–847. 7459: 7440:(3): 193–203. 7424: 7405:(3): 265–277. 7389: 7382: 7364: 7357: 7339: 7304: 7253: 7246: 7228: 7185: 7178: 7156: 7117: 7098: 7076: 7057: 7035: 7000: 6978: 6953: 6902: 6867: 6860: 6842: 6831: 6801: 6740: 6699: 6658: 6639:(3): 275–285. 6623: 6608: 6582: 6561:(1): 150–158. 6538: 6502: 6483: 6461: 6434:(4): 307–319. 6418: 6369: 6328: 6321: 6303: 6292: 6262: 6255: 6237: 6194: 6175: 6150: 6131:(1–2): 79–99. 6115: 6066: 6047:(5): 339–356. 6031: 6012:(6): 663–672. 5996: 5944: 5909: 5866: 5831: 5824: 5803: 5760: 5701: 5658: 5631: 5612:(5): 937–940. 5596: 5561: 5546: 5520: 5513: 5495: 5468:(4): 457–464. 5449: 5414: 5387: 5348: 5333: 5314:(5): 733–746. 5293: 5255: 5248: 5230: 5223: 5205: 5198: 5169: 5162: 5144: 5091: 5084: 5063: 5024: 5017: 4991: 4984: 4963: 4956: 4923: 4892: 4873: 4853: 4815: 4761: 4742: 4720: 4701: 4679: 4620: 4601: 4576: 4549:(2): 111–165. 4533: 4498: 4447: 4440: 4422: 4403:(12): 536–44. 4384: 4365: 4338: 4284: 4277: 4243: 4242: 4240: 4237: 4236: 4235: 4229: 4226:Antimetabolite 4223: 4218:– a branch of 4212: 4211: 4208:Biology portal 4195: 4192: 4108: 4105: 4097:photosynthesis 4067:The herbicide 4064: 4061: 4021:synaptic cleft 4017:norepinephrine 3984: 3981: 3955:used to treat 3940: 3937: 3917:ribbon diagram 3909:transpeptidase 3857: 3854: 3753:prostaglandins 3749:cyclooxygenase 3716: 3713: 3691:, such as the 3662:alpha-amanitin 3613:glycoalkaloids 3553:seed predation 3551:To discourage 3544: 3541: 3463:Metabolic flux 3454: 3451: 3397: 3394: 3349:biosynthesis, 3288: 3285: 3251: 3248: 3216: 3209: 3189: 3176: 3169: 3168: 3167: 3163: 3162: 3161: 3160: 3158: 3155: 3150: 3143: 3136: 3129: 3122: 3115: 3108: 3004: 2997: 2996: 2985: 2978: 2977: 2976: 2972: 2971: 2970: 2969: 2967: 2964: 2962: 2959: 2954:protein kinase 2922: 2901:peptidomimetic 2891:used to treat 2875: 2872: 2821: 2814: 2813: 2812: 2803: 2796: 2795: 2794: 2789: 2782: 2781: 2780: 2779: 2778: 2776: 2773: 2764: 2757: 2750: 2743: 2732: 2729: 2710: 2707: 2702: 2695: 2687: 2684: 2682: 2679: 2674: 2667: 2660: 2649: 2615: 2608: 2601: 2594: 2588: 2587: 2576: 2569: 2564: 2560: 2555: 2552: 2549: 2543: 2540: 2537: 2532: 2528: 2517: 2502: 2498: 2493: 2490: 2487: 2481: 2478: 2475: 2472: 2458: 2457: 2443: 2440: 2437: 2434: 2429: 2425: 2421: 2416: 2412: 2407: 2403: 2400: 2395: 2392: 2389: 2384: 2381: 2378: 2374: 2370: 2365: 2361: 2356: 2352: 2349: 2343: 2337: 2334: 2331: 2326: 2322: 2318: 2313: 2309: 2305: 2300: 2297: 2294: 2289: 2286: 2283: 2279: 2272: 2269: 2253:to a modified 2242: 2235: 2224: 2217: 2210: 2203: 2196: 2178: 2175: 2174: 2173: 2155: 2151: 2147: 2144: 2136: 2123: 2117: 2105: 2100: 2097: 2093: 2089: 2084: 2081: 2077: 2073: 2070: 2065: 2062: 2058: 2042: 2035: 2027: 2020: 2013: 2012: 1994: 1990: 1986: 1983: 1975: 1962: 1956: 1944: 1939: 1936: 1932: 1928: 1923: 1920: 1916: 1912: 1909: 1904: 1901: 1897: 1880: 1873: 1872: 1854: 1850: 1846: 1843: 1835: 1822: 1816: 1804: 1799: 1796: 1792: 1788: 1783: 1780: 1776: 1772: 1769: 1764: 1761: 1757: 1742: 1741: 1723: 1719: 1715: 1712: 1704: 1691: 1685: 1671: 1667: 1663: 1660: 1655: 1651: 1635: 1628: 1627: 1609: 1605: 1601: 1598: 1590: 1577: 1571: 1548: 1547: 1529: 1525: 1521: 1518: 1510: 1497: 1491: 1465: 1464: 1447: 1443: 1434: 1426: 1418: 1415: 1410: 1406: 1392: 1386: 1372: 1368: 1364: 1359: 1355: 1351: 1348: 1346: 1344: 1341: 1338: 1330: 1322: 1319: 1314: 1310: 1297: 1289: 1286: 1281: 1277: 1263:simplify 1260: 1256: 1247: 1239: 1236: 1231: 1227: 1214: 1206: 1195: 1192: 1188: 1181: 1177: 1172: 1169: 1167: 1165: 1157: 1154: 1151: 1143: 1140: 1137: 1129: 1121: 1117: 1109: 1101: 1098: 1093: 1089: 1076: 1068: 1065: 1062: 1054: 1051: 1046: 1042: 1030: 1023: 1019: 1014: 1011: 1009: 1007: 1004: 1001: 991: 987: 972: 968: 951: 947: 939: 931: 928: 923: 919: 904: 900: 888: 881: 877: 872: 869: 867: 853: 849: 835: 829: 817: 814: 800: 796: 784: 783: 768: 761: 751: 750: 746: 739: 732: 725: 719: 715: 708: 701: 694: 688: 684: 677: 670: 663: 657: 653: 646: 635: 628: 605: 602: 592:(that is, the 572: 569: 563: 556: 541: 538: 532: 521: 514: 504: 501: 491: 484: 477: 470: 455: 452: 446: 439: 404:hydrogen bonds 390: 389: 384: 377: 376: 372: 365: 364: 363: 359: 358: 357: 356: 354: 351: 248: 245: 195:used to treat 161:drug molecules 118:non-covalently 76:necessary for 72:that speed up 68:. Enzymes are 26: 9: 6: 4: 3: 2: 10455: 10444: 10441: 10439: 10436: 10434: 10431: 10429: 10426: 10425: 10423: 10407: 10403: 10402: 10397: 10394: 10390: 10389: 10384: 10381: 10377: 10376: 10371: 10368: 10364: 10363: 10358: 10355: 10351: 10350: 10345: 10342: 10338: 10337: 10332: 10329: 10325: 10324: 10319: 10318: 10316: 10312: 10306: 10303: 10301: 10298: 10296: 10293: 10291: 10288: 10286: 10283: 10282: 10280: 10276: 10270: 10267: 10265: 10264:Enzyme family 10262: 10260: 10257: 10255: 10252: 10251: 10249: 10245: 10239: 10236: 10234: 10231: 10229: 10228:Cooperativity 10226: 10224: 10221: 10220: 10218: 10214: 10208: 10205: 10203: 10200: 10198: 10195: 10193: 10190: 10188: 10187:Oxyanion hole 10185: 10183: 10180: 10178: 10175: 10173: 10170: 10169: 10167: 10163: 10159: 10152: 10147: 10145: 10140: 10138: 10133: 10132: 10129: 10117: 10114: 10112: 10111:Pharmacophore 10109: 10107: 10104: 10102: 10099: 10097: 10094: 10092: 10089: 10087: 10084: 10082: 10079: 10077: 10074: 10072: 10069: 10067: 10064: 10062: 10059: 10057: 10054: 10052: 10049: 10047: 10044: 10042: 10039: 10037: 10036:Drug delivery 10034: 10032: 10029: 10027: 10026:Chemogenomics 10024: 10022: 10019: 10017: 10014: 10013: 10010: 10006: 9998: 9993: 9991: 9986: 9984: 9979: 9978: 9975: 9959: 9956: 9955: 9953: 9951:Miscellaneous 9949: 9943: 9939: 9938: 9935: 9931: 9930: 9928: 9925: 9921: 9915: 9912: 9910: 9906: 9905: 9900: 9897: 9895: 9892: 9890: 9889:Enkephalinase 9887: 9886: 9885: 9882: 9878: 9875: 9873: 9870: 9869: 9868: 9867:Endopeptidase 9865: 9861: 9858: 9856: 9853: 9852: 9851: 9847: 9843: 9842: 9839: 9836: 9834: 9833:Neuraminidase 9831: 9829: 9825: 9824: 9821: 9818: 9816: 9813: 9811: 9807: 9806: 9804: 9801: 9797: 9787: 9784: 9783: 9782: 9779: 9778: 9777: 9774: 9770: 9767: 9765: 9762: 9761: 9760: 9756: 9755: 9752: 9748: 9747: 9744: 9741: 9739: 9735: 9734: 9731: 9727: 9726: 9723: 9720: 9718: 9714: 9713: 9711: 9708: 9704: 9698: 9695: 9693: 9689: 9688: 9685: 9682: 9680: 9676: 9675: 9672: 9668: 9667: 9664: 9660: 9659: 9656: 9652: 9651: 9648: 9644: 9643: 9640: 9637: 9635: 9631: 9630: 9628: 9625: 9621: 9618: 9614: 9608: 9605: 9603: 9600: 9598: 9595: 9593: 9590: 9588: 9585: 9584: 9582: 9578: 9574: 9570: 9563: 9558: 9556: 9551: 9549: 9544: 9543: 9540: 9531: 9527: 9523: 9518: 9514: 9510: 9505: 9501: 9497: 9496: 9483: 9479: 9474: 9469: 9464: 9459: 9455: 9451: 9447: 9440: 9432: 9428: 9424: 9420: 9416: 9412: 9408: 9404: 9397: 9389: 9383: 9379: 9372: 9364: 9360: 9356: 9352: 9347: 9342: 9338: 9334: 9330: 9323: 9315: 9311: 9306: 9301: 9297: 9293: 9290:(6): 489–96. 9289: 9285: 9281: 9274: 9266: 9262: 9258: 9254: 9250: 9246: 9239: 9231: 9227: 9223: 9219: 9215: 9211: 9204: 9196: 9192: 9188: 9184: 9180: 9176: 9169: 9161: 9154: 9146: 9142: 9138: 9134: 9129: 9124: 9120: 9116: 9112: 9105: 9097: 9091: 9087: 9080: 9072: 9068: 9063: 9058: 9054: 9050: 9046: 9042: 9038: 9034: 9030: 9023: 9016: 9004: 9000: 8994: 8990: 8986: 8982: 8978: 8971: 8963: 8959: 8955: 8951: 8947: 8943: 8939: 8935: 8928: 8920: 8916: 8912: 8908: 8904: 8900: 8893: 8877: 8873: 8872: 8864: 8856: 8852: 8847: 8842: 8838: 8834: 8830: 8826: 8822: 8815: 8799: 8795: 8789: 8785: 8781: 8774: 8766: 8760: 8756: 8749: 8741: 8735: 8731: 8724: 8716: 8712: 8708: 8704: 8700: 8696: 8692: 8688: 8681: 8673: 8669: 8665: 8661: 8656: 8651: 8647: 8643: 8639: 8635: 8631: 8624: 8616: 8612: 8607: 8602: 8598: 8594: 8590: 8586: 8582: 8575: 8567: 8563: 8559: 8555: 8551: 8547: 8543: 8539: 8532: 8524: 8520: 8516: 8512: 8508: 8504: 8500: 8496: 8489: 8481: 8477: 8473: 8467: 8462: 8457: 8453: 8446: 8438: 8434: 8429: 8424: 8420: 8416: 8412: 8408: 8404: 8397: 8389: 8385: 8381: 8377: 8373: 8369: 8365: 8361: 8354: 8338: 8334: 8330: 8326: 8322: 8318: 8311: 8303: 8299: 8294: 8289: 8285: 8281: 8277: 8273: 8269: 8262: 8254: 8250: 8246: 8242: 8238: 8234: 8227: 8211: 8207: 8203: 8199: 8195: 8191: 8187: 8183: 8179: 8175: 8168: 8160: 8156: 8151: 8146: 8142: 8138: 8134: 8127: 8119: 8115: 8111: 8107: 8103: 8099: 8095: 8091: 8084: 8076: 8072: 8068: 8064: 8060: 8056: 8049: 8041: 8037: 8033: 8029: 8025: 8021: 8017: 8013: 8006: 7998: 7994: 7989: 7984: 7980: 7976: 7972: 7968: 7964: 7957: 7950: 7945: 7941: 7936: 7931: 7927: 7923: 7919: 7915: 7911: 7904: 7902: 7885: 7881: 7875: 7871: 7867: 7860: 7858: 7849: 7845: 7841: 7837: 7834:(1–2): 1–14. 7833: 7829: 7822: 7814: 7810: 7805: 7800: 7795: 7790: 7786: 7782: 7778: 7771: 7763: 7759: 7754: 7749: 7744: 7739: 7735: 7731: 7727: 7720: 7712: 7706: 7702: 7698: 7694: 7687: 7679: 7675: 7671: 7667: 7660: 7652: 7648: 7644: 7640: 7636: 7632: 7625: 7617: 7613: 7609: 7605: 7601: 7597: 7593: 7589: 7582: 7574: 7570: 7566: 7562: 7558: 7554: 7550: 7546: 7539: 7531: 7527: 7523: 7519: 7514: 7509: 7505: 7501: 7497: 7490: 7482: 7478: 7474: 7470: 7463: 7455: 7451: 7447: 7443: 7439: 7435: 7428: 7420: 7416: 7412: 7408: 7404: 7400: 7393: 7385: 7379: 7375: 7368: 7360: 7354: 7350: 7343: 7335: 7331: 7327: 7323: 7319: 7315: 7308: 7292: 7288: 7284: 7280: 7276: 7272: 7268: 7264: 7257: 7249: 7243: 7239: 7232: 7224: 7220: 7216: 7212: 7208: 7204: 7200: 7196: 7189: 7181: 7175: 7171: 7167: 7160: 7144: 7140: 7136: 7132: 7128: 7121: 7105: 7101: 7095: 7091: 7087: 7080: 7064: 7060: 7054: 7050: 7046: 7039: 7031: 7027: 7023: 7019: 7015: 7011: 7004: 6985: 6981: 6975: 6971: 6964: 6957: 6949: 6945: 6940: 6935: 6930: 6925: 6921: 6917: 6913: 6906: 6898: 6894: 6890: 6886: 6882: 6878: 6871: 6863: 6857: 6853: 6846: 6838: 6834: 6828: 6824: 6820: 6816: 6812: 6805: 6797: 6793: 6788: 6783: 6778: 6773: 6769: 6765: 6761: 6754: 6750: 6744: 6736: 6732: 6727: 6722: 6718: 6714: 6710: 6703: 6695: 6691: 6686: 6681: 6677: 6673: 6669: 6662: 6654: 6650: 6646: 6642: 6638: 6634: 6627: 6619: 6615: 6611: 6605: 6601: 6597: 6593: 6586: 6578: 6574: 6569: 6564: 6560: 6556: 6552: 6545: 6543: 6534: 6530: 6526: 6522: 6518: 6514: 6506: 6490: 6486: 6480: 6476: 6472: 6465: 6457: 6453: 6449: 6445: 6441: 6437: 6433: 6429: 6422: 6414: 6410: 6405: 6400: 6396: 6392: 6388: 6384: 6383:AAPS PharmSci 6380: 6373: 6365: 6361: 6356: 6351: 6347: 6343: 6339: 6332: 6324: 6318: 6314: 6307: 6300: 6295: 6289: 6285: 6281: 6277: 6273: 6266: 6258: 6252: 6248: 6241: 6233: 6229: 6225: 6221: 6217: 6213: 6209: 6205: 6198: 6182: 6178: 6172: 6168: 6164: 6157: 6155: 6146: 6142: 6138: 6134: 6130: 6126: 6119: 6111: 6107: 6102: 6097: 6093: 6089: 6086:(1): 175–89. 6085: 6081: 6077: 6070: 6062: 6058: 6054: 6050: 6046: 6042: 6035: 6027: 6023: 6019: 6015: 6011: 6007: 6000: 5992: 5988: 5983: 5978: 5974: 5970: 5966: 5962: 5958: 5951: 5949: 5940: 5936: 5932: 5928: 5924: 5920: 5913: 5905: 5901: 5897: 5893: 5889: 5885: 5881: 5877: 5870: 5862: 5858: 5854: 5850: 5846: 5842: 5835: 5827: 5821: 5817: 5810: 5808: 5799: 5795: 5791: 5787: 5783: 5779: 5775: 5771: 5764: 5756: 5752: 5747: 5742: 5737: 5732: 5728: 5724: 5720: 5716: 5712: 5705: 5697: 5693: 5689: 5685: 5681: 5677: 5673: 5669: 5662: 5654: 5650: 5646: 5642: 5635: 5627: 5623: 5619: 5615: 5611: 5607: 5600: 5592: 5588: 5584: 5580: 5576: 5572: 5565: 5557: 5553: 5549: 5547:9780121821500 5543: 5539: 5535: 5531: 5524: 5516: 5510: 5506: 5499: 5491: 5487: 5483: 5479: 5475: 5471: 5467: 5463: 5456: 5454: 5445: 5441: 5437: 5433: 5429: 5425: 5418: 5410: 5406: 5402: 5398: 5397:BioTechniques 5391: 5375: 5371: 5367: 5363: 5359: 5352: 5344: 5337: 5329: 5325: 5321: 5317: 5313: 5309: 5302: 5300: 5298: 5289: 5285: 5281: 5277: 5273: 5269: 5262: 5260: 5251: 5245: 5241: 5234: 5226: 5220: 5216: 5209: 5201: 5195: 5191: 5184: 5182: 5180: 5178: 5176: 5174: 5165: 5159: 5155: 5148: 5141: 5136: 5132: 5128: 5124: 5119: 5114: 5110: 5106: 5102: 5095: 5087: 5081: 5077: 5070: 5068: 5051: 5047: 5043: 5039: 5035: 5028: 5020: 5014: 5010: 5006: 5002: 4995: 4987: 4981: 4977: 4970: 4968: 4959: 4953: 4949: 4942: 4940: 4938: 4936: 4934: 4932: 4930: 4928: 4911: 4907: 4901: 4899: 4897: 4880: 4876: 4870: 4866: 4865: 4857: 4849: 4845: 4841: 4837: 4833: 4829: 4822: 4820: 4811: 4807: 4802: 4797: 4793: 4789: 4785: 4781: 4777: 4770: 4768: 4766: 4749: 4745: 4739: 4735: 4731: 4724: 4708: 4704: 4698: 4694: 4690: 4683: 4675: 4671: 4666: 4661: 4656: 4651: 4647: 4643: 4639: 4635: 4631: 4624: 4608: 4604: 4598: 4594: 4590: 4583: 4581: 4572: 4568: 4564: 4560: 4556: 4552: 4548: 4544: 4537: 4529: 4525: 4521: 4517: 4513: 4509: 4502: 4494: 4490: 4485: 4480: 4475: 4470: 4466: 4462: 4458: 4451: 4443: 4437: 4433: 4426: 4418: 4414: 4410: 4406: 4402: 4398: 4391: 4389: 4372: 4368: 4362: 4358: 4354: 4347: 4345: 4343: 4334: 4330: 4325: 4320: 4316: 4312: 4309:(127): 1–13. 4308: 4304: 4300: 4293: 4291: 4289: 4280: 4274: 4270: 4266: 4262: 4255: 4253: 4251: 4249: 4244: 4233: 4230: 4227: 4224: 4221: 4217: 4214: 4213: 4209: 4203: 4198: 4191: 4189: 4185: 4181: 4177: 4173: 4169: 4164: 4162: 4158: 4153: 4149: 4144: 4142: 4138: 4133: 4129: 4124: 4122: 4113: 4104: 4102: 4098: 4094: 4090: 4086: 4082: 4078: 4077:sulfonylureas 4074: 4070: 4060: 4058: 4054: 4050: 4046: 4042: 4038: 4034: 4030: 4029:physostigmine 4026: 4022: 4018: 4014: 4010: 4006: 4002: 3998: 3997:acetylcholine 3994: 3990: 3980: 3978: 3974: 3970: 3966: 3962: 3958: 3954: 3950: 3946: 3936: 3934: 3930: 3925: 3920: 3918: 3914: 3910: 3905: 3901: 3897: 3893: 3892:peptidoglycan 3889: 3880: 3876: 3871: 3862: 3853: 3851: 3847: 3843: 3839: 3835: 3830: 3828: 3824: 3820: 3816: 3812: 3807: 3805: 3801: 3797: 3794:in including 3793: 3789: 3785: 3781: 3780:Janus kinases 3777: 3773: 3769: 3765: 3761: 3756: 3754: 3750: 3746: 3742: 3734: 3729: 3721: 3712: 3710: 3706: 3702: 3698: 3694: 3690: 3689:antinutrients 3685: 3683: 3679: 3675: 3671: 3667: 3663: 3658: 3656: 3652: 3648: 3647: 3642: 3638: 3637:Neurotoxicity 3634: 3630: 3626: 3622: 3618: 3614: 3609: 3605: 3600: 3598: 3594: 3590: 3587: 3583: 3579: 3574: 3570: 3562: 3558: 3554: 3549: 3540: 3538: 3534: 3529: 3524: 3520: 3516: 3511: 3509: 3505: 3500: 3496: 3492: 3488: 3484: 3481:and produces 3480: 3476: 3472: 3468: 3464: 3460: 3450: 3448: 3444: 3440: 3439:acetylcholine 3436: 3432: 3428: 3427:disinfectants 3424: 3420: 3416: 3412: 3407: 3403: 3393: 3391: 3387: 3383: 3382: 3377: 3371: 3369: 3364: 3360: 3356: 3352: 3348: 3344: 3340: 3334: 3330: 3326: 3322: 3318: 3310: 3306: 3301: 3297: 3293: 3287:Some examples 3284: 3282: 3278: 3274: 3270: 3261: 3256: 3247: 3245: 3241: 3237: 3233: 3229: 3225: 3220: 3215: 3208: 3203: 3202:rate equation 3199: 3193: 3188: 3173: 3154: 3149: 3142: 3135: 3128: 3121: 3114: 3105: 3103: 3102:peptide bonds 3099: 3095: 3091: 3085: 3083: 3079: 3075: 3071: 3067: 3063: 3059: 3055: 3051: 3047: 3046:electrophilic 3043: 3039: 3035: 3031: 3027: 3023: 3019: 3015: 3001: 2993: 2990:(DFP) with a 2989: 2982: 2958: 2955: 2950: 2948: 2943: 2938: 2936: 2935:neuraminidase 2932: 2928: 2921: 2917: 2912: 2910: 2906: 2905:peptide bonds 2902: 2898: 2894: 2890: 2886: 2882: 2871: 2869: 2865: 2861: 2857: 2853: 2848: 2844: 2840: 2837:reactions of 2836: 2825: 2818: 2807: 2800: 2786: 2772: 2770: 2763: 2756: 2749: 2742: 2738: 2728: 2726: 2722: 2717: 2706: 2701: 2694: 2681:Special cases 2678: 2673: 2666: 2659: 2655: 2648: 2644: 2640: 2636: 2632: 2631:Eadie-Hofstee 2628: 2623: 2621: 2614: 2607: 2604:become (α/α') 2600: 2593: 2574: 2562: 2558: 2550: 2541: 2538: 2535: 2526: 2518: 2500: 2496: 2488: 2479: 2476: 2473: 2470: 2463: 2462: 2461: 2438: 2432: 2427: 2423: 2410: 2405: 2401: 2390: 2382: 2379: 2376: 2372: 2359: 2354: 2350: 2341: 2332: 2320: 2316: 2311: 2307: 2303: 2295: 2287: 2284: 2281: 2277: 2270: 2267: 2260: 2259: 2258: 2256: 2252: 2248: 2241: 2234: 2230: 2223: 2216: 2209: 2202: 2195: 2192: 2183: 2153: 2149: 2145: 2098: 2095: 2091: 2087: 2082: 2079: 2075: 2068: 2063: 2060: 2056: 2048: 2047: 2046: 2041: 2034: 2026: 2019: 1992: 1988: 1984: 1937: 1930: 1926: 1921: 1914: 1907: 1902: 1895: 1887: 1886: 1885: 1879: 1852: 1848: 1844: 1797: 1790: 1786: 1781: 1774: 1767: 1762: 1755: 1747: 1746: 1745: 1721: 1717: 1713: 1665: 1658: 1649: 1641: 1640: 1639: 1634: 1607: 1603: 1599: 1553: 1552: 1551: 1527: 1523: 1519: 1473: 1472: 1471: 1468: 1441: 1413: 1408: 1404: 1366: 1362: 1353: 1349: 1347: 1339: 1336: 1317: 1312: 1308: 1284: 1279: 1275: 1254: 1234: 1229: 1225: 1193: 1190: 1186: 1175: 1170: 1168: 1155: 1152: 1138: 1115: 1096: 1091: 1087: 1063: 1049: 1044: 1040: 1028: 1017: 1012: 1010: 1002: 999: 989: 985: 970: 966: 945: 926: 921: 917: 902: 898: 886: 875: 870: 868: 851: 847: 815: 812: 794: 774: 773: 772: 767: 760: 755: 745: 738: 731: 724: 720: 714: 707: 700: 693: 689: 683: 676: 669: 662: 658: 652: 645: 641: 640: 639: 634: 627: 624: 619: 615: 611: 601: 597: 595: 591: 587: 583: 578: 568: 566: 559: 551: 547: 537: 535: 528: 524: 517: 510: 503:Uncompetitive 500: 498: 494: 487: 480: 473: 466: 461: 451: 449: 442: 435: 430: 428: 424: 419: 417: 413: 409: 405: 401: 381: 369: 350: 348: 344: 340: 336: 332: 328: 324: 319: 316: 312: 308: 304: 300: 299:ribonucleases 296: 292: 288: 284: 280: 275: 273: 269: 265: 260: 258: 254: 244: 242: 238: 234: 230: 229:kidney damage 226: 222: 218: 214: 210: 206: 202: 198: 194: 190: 186: 182: 178: 174: 170: 166: 162: 157: 155: 151: 147: 143: 139: 135: 131: 127: 122: 119: 115: 114:chemical bond 111: 107: 101: 99: 95: 91: 87: 83: 79: 75: 71: 67: 63: 59: 55: 47: 43: 39: 34: 30: 19: 10401:Translocases 10398: 10385: 10372: 10359: 10346: 10336:Transferases 10333: 10320: 10232: 10177:Binding site 10106:Pharmacology 10060: 9883: 9850:Exopeptidase 9820:Ribonuclease 9786:Janus kinase 9671:Lipoxygenase 9647:5α-Reductase 9572: 9569:Pharmacology 9530:the original 9516: 9453: 9449: 9439: 9406: 9402: 9396: 9377: 9371: 9336: 9332: 9322: 9287: 9283: 9273: 9248: 9244: 9238: 9213: 9209: 9203: 9178: 9174: 9168: 9159: 9153: 9118: 9114: 9104: 9085: 9079: 9036: 9032: 9022: 9014: 9007:. Retrieved 8980: 8970: 8937: 8933: 8927: 8902: 8898: 8892: 8880:. Retrieved 8870: 8863: 8828: 8824: 8814: 8802:. Retrieved 8783: 8773: 8754: 8748: 8729: 8723: 8690: 8686: 8680: 8637: 8633: 8623: 8588: 8584: 8574: 8541: 8537: 8531: 8498: 8494: 8488: 8451: 8445: 8410: 8406: 8396: 8363: 8359: 8353: 8341:. Retrieved 8324: 8320: 8310: 8278:(1): 29–56. 8275: 8271: 8261: 8239:(9): 602–5. 8236: 8232: 8226: 8214:. Retrieved 8181: 8177: 8167: 8140: 8136: 8126: 8093: 8089: 8083: 8058: 8054: 8048: 8015: 8011: 8005: 7970: 7966: 7956: 7947: 7917: 7913: 7888:. Retrieved 7870:Pharmacology 7869: 7831: 7827: 7821: 7784: 7780: 7770: 7733: 7729: 7719: 7692: 7686: 7669: 7665: 7659: 7634: 7630: 7624: 7594:(1): 13–24. 7591: 7587: 7581: 7548: 7544: 7538: 7503: 7499: 7489: 7472: 7468: 7462: 7437: 7433: 7427: 7402: 7398: 7392: 7373: 7367: 7348: 7342: 7317: 7313: 7307: 7295:. Retrieved 7270: 7266: 7256: 7237: 7231: 7198: 7194: 7188: 7169: 7159: 7147:. Retrieved 7130: 7120: 7108:. Retrieved 7089: 7079: 7067:. Retrieved 7048: 7038: 7013: 7009: 7003: 6991:. Retrieved 6969: 6956: 6919: 6915: 6905: 6880: 6876: 6870: 6852:Pharmacology 6851: 6845: 6837:the original 6814: 6804: 6767: 6763: 6743: 6716: 6712: 6702: 6678:(1): 65–72. 6675: 6671: 6661: 6636: 6632: 6626: 6591: 6585: 6558: 6554: 6519:(1): 83–91. 6516: 6512: 6505: 6493:. Retrieved 6474: 6464: 6431: 6427: 6421: 6389:(1): 68–77. 6386: 6382: 6372: 6348:(1): 81–95. 6345: 6341: 6331: 6312: 6306: 6297: 6275: 6271: 6265: 6246: 6240: 6207: 6203: 6197: 6185:. Retrieved 6166: 6128: 6124: 6118: 6083: 6079: 6069: 6044: 6040: 6034: 6009: 6005: 5999: 5964: 5960: 5922: 5918: 5912: 5879: 5875: 5869: 5844: 5840: 5834: 5815: 5773: 5769: 5763: 5718: 5714: 5704: 5671: 5667: 5661: 5644: 5640: 5634: 5609: 5605: 5599: 5577:(1): 65–66. 5574: 5570: 5564: 5529: 5523: 5504: 5498: 5465: 5461: 5427: 5423: 5417: 5400: 5396: 5390: 5378:. Retrieved 5361: 5351: 5342: 5336: 5311: 5307: 5271: 5267: 5239: 5233: 5214: 5208: 5189: 5153: 5147: 5138: 5108: 5104: 5094: 5075: 5054:. Retrieved 5037: 5027: 5000: 4994: 4975: 4947: 4914:. Retrieved 4910:the original 4883:. Retrieved 4864:Biochemistry 4863: 4856: 4831: 4827: 4783: 4780:Biochemistry 4779: 4752:. Retrieved 4733: 4723: 4711:. Retrieved 4692: 4682: 4637: 4633: 4623: 4611:. Retrieved 4592: 4546: 4542: 4536: 4511: 4508:Biochemistry 4507: 4501: 4464: 4460: 4450: 4431: 4425: 4400: 4396: 4375:. Retrieved 4356: 4306: 4302: 4260: 4165: 4145: 4125: 4118: 4066: 4057:chlorpyrifos 3986: 3942: 3921: 3913:Streptomyces 3912: 3885: 3870:Streptomyces 3869: 3831: 3811:methotrexate 3808: 3757: 3738: 3686: 3682:algal blooms 3659: 3644: 3631:), that are 3601: 3597:cytoskeleton 3593:microtubules 3566: 3512: 3456: 3443:nerve agents 3411:insecticides 3399: 3396:Applications 3385: 3379: 3372: 3341: 3315: 3299: 3273:methotrexate 3265: 3259: 3250:Slow binding 3221: 3213: 3206: 3194: 3186: 3183: 3147: 3140: 3133: 3126: 3119: 3112: 3106: 3094:denaturation 3086: 3054:nucleophiles 3011: 2973:DFP reaction 2951: 2939: 2919: 2913: 2877: 2831: 2761: 2754: 2747: 2740: 2734: 2712: 2699: 2692: 2689: 2671: 2664: 2657: 2653: 2646: 2642: 2638: 2624: 2612: 2605: 2598: 2591: 2589: 2459: 2239: 2232: 2221: 2214: 2207: 2200: 2193: 2188: 2039: 2032: 2024: 2017: 2014: 1877: 1874: 1743: 1632: 1629: 1549: 1469: 1466: 765: 758: 756: 752: 743: 736: 729: 722: 712: 705: 698: 691: 681: 674: 667: 660: 650: 643: 632: 625: 607: 598: 590:conformation 588:changes the 574: 561: 554: 543: 530: 519: 512: 506: 489: 482: 475: 468: 464: 457: 444: 437: 431: 426: 420: 397: 343:conformation 323:binding site 320: 290: 286: 282: 276: 261: 250: 241:pharmacology 237:biochemistry 185:chemotherapy 181:methotrexate 158: 123: 102: 88:. An enzyme 53: 51: 29: 10172:Active site 10041:Drug design 9899:Oxytocinase 9707:Transferase 9456:(6): 3232. 9039:: 263–271. 8934:Amino Acids 8693:: 116–124. 7201:(1): 1–14. 7131:StatPearls 6883:: 493–535. 5641:Tetrahedron 4834:: 173–187. 4093:carotenoids 4085:amino acids 4033:neostigmine 4025:edrophonium 3933:fatty acids 3924:drug design 3922:Antibiotic 3896:antibiotics 3856:Antibiotics 3768:cell growth 3709:glycosidase 3674:microcystin 3604:neurotoxins 3467:metabolites 3325:active site 3277:allopurinol 3026:haloalkanes 2931:oxonium ion 2927:oseltamivir 2866:(NADH) and 2760:) and off ( 454:Competitive 416:active site 412:ionic bonds 347:kinetically 335:orthosteric 331:active site 268:homeostasis 94:active site 90:facilitates 80:, in which 10438:Metabolism 10422:Categories 10375:Isomerases 10349:Hydrolases 10216:Regulation 10031:Drug class 10003:Topics in 9339:: 127851. 8480:1240584737 8184:: 112262. 7787:(6): 350. 7736:(6): 324. 7195:BioFactors 5140:substrate. 5038:StatPearls 4239:References 4220:proteomics 4069:glyphosate 4063:Herbicides 3989:pesticides 3983:Pesticides 3971:targeting 3939:Antivirals 3904:vancomycin 3900:penicillin 3868:G and the 3838:sildenafil 3827:nucleotide 3815:folic acid 3733:sildenafil 3619:(includes 3617:Solanaceae 3578:paclitaxel 3423:glyphosate 3419:herbicides 3062:sulfhydryl 3014:covalently 2947:peptidases 2942:tipranavir 2824:tipranavir 2731:Slow-tight 2611:and (1/α') 582:allosteric 392:catalysis. 339:allosteric 311:N-terminal 231:and other 191:) and the 167:such as a 110:reversibly 42:substrates 10254:EC number 9800:Hydrolase 9764:Integrase 9679:Aromatase 9616:Substrate 9513:"PubChem" 9431:226271153 9363:232059044 9145:231633284 8672:212651676 8523:195356119 8388:231761270 8327:(6): 98. 8272:Infection 8206:214809706 8040:237311419 6756:; 4885:31 August 4571:215772580 4168:optimised 4053:parathion 4049:malathion 4041:carbamate 4009:serotonin 3973:influenza 3929:ribosomes 3888:cell wall 3823:thymidine 3796:arthritis 3666:death cap 3608:paralysis 3576:example, 3475:catabolic 3431:triclosan 3415:malathion 3402:metabolic 3355:ornithine 3347:polyamine 3302:, 2004. ( 3281:acyclovir 3228:MALDI-TOF 3157:Measuring 3078:threonine 3022:aldehydes 2897:ritonavir 2856:isoniazid 2806:ritonavir 2568:′ 2531:′ 2527:α 2471:α 2415:′ 2411:α 2402:α 2364:′ 2360:α 2325:′ 2321:α 2304:α 2206:'. Hence 2088:− 2069:− 1927:− 1908:− 1787:− 1768:− 1662:Δ 1659:− 1363:− 1194:− 1139:− 1124:add 1064:− 327:substrate 209:pathogens 205:analogous 183:(used in 173:bacterium 154:predators 146:nucleases 142:proteases 106:catalysis 10278:Kinetics 10202:Cofactor 10165:Activity 9846:Protease 9504:Archived 9500:"BRENDA" 9482:33810118 9423:33155894 9355:33631371 9314:17959370 9265:16713909 9230:12203463 9195:16796557 9137:33454380 9003:Archived 8954:16547651 8919:28117022 8876:Archived 8855:29655452 8798:Archived 8715:53763831 8707:30472161 8664:32152244 8615:35847492 8558:29595065 8515:31237209 8437:27668701 8380:33501747 8337:Archived 8333:16711368 8302:33367978 8253:17894443 8210:Archived 8198:32248005 8159:10913932 8118:52945888 8110:30301707 8075:14529544 8032:34454676 7997:30259761 7944:27910877 7890:14 April 7884:Archived 7848:15450171 7813:31216687 7762:31174319 7678:11577938 7651:12369866 7573:36465515 7565:15572604 7530:13701908 7522:29734182 7454:12769688 7419:16515527 7297:14 April 7291:Archived 7287:15246086 7223:24586866 7215:10475585 7149:14 April 7143:Archived 7139:30571049 7110:14 April 7104:Archived 7063:Archived 7030:16041744 6984:Archived 6948:15102853 6796:15102853 6533:22902804 6489:Archived 6456:11766917 6448:10398927 6413:11741224 6364:11182321 6232:56480231 6224:30565923 6181:Archived 6145:16182621 6110:25494294 6061:14529528 6026:10702632 5991:30335982 5939:21864279 5904:25269012 5896:29149530 5861:16611117 5798:21808708 5790:19912064 5755:20194791 5409:11464510 5374:Archived 5370:22553872 5328:17307293 5288:22038120 5135:73480979 5127:30811960 5050:Archived 5046:31424826 4879:Archived 4848:14021668 4810:29689165 4748:Archived 4707:Archived 4674:30917186 4634:PLOS ONE 4607:Archived 4563:32290726 4493:30809526 4417:12821301 4377:14 April 4371:Archived 4333:28202588 4194:See also 4013:dopamine 3957:HIV/AIDS 3951:include 3898:such as 3882:) 3776:imatinib 3774:such as 3735:(Viagra) 3641:atropine 3629:eggplant 3559:contain 3519:zymogens 3515:pancreas 3491:pyruvate 3429:such as 3421:such as 3413:such as 3333:synapses 3312:) 3244:peptides 3238:such as 3236:protease 3146:) where 3082:tyrosine 3074:cysteine 3058:hydroxyl 3056:such as 3044:. These 2893:HIV/AIDS 2874:Examples 2852:entropic 2716:kinetics 550:activity 423:dialysis 402:such as 307:zymogens 289:rotease 257:proteins 201:specific 197:HIV/AIDS 177:parasite 165:pathogen 86:products 70:proteins 66:activity 58:molecule 46:products 10388:Ligases 10158:Enzymes 9872:Trypsin 9473:8004986 9305:4441723 9071:1980104 9062:1567841 9053:3431034 9009:27 June 8962:2358278 8882:9 April 8846:6690491 8804:21 July 8655:8725622 8606:9279714 8566:4489039 8428:5364071 8343:9 April 8293:7851017 8216:20 July 7988:6322661 7935:6314433 7804:6628406 7753:6628454 7616:9604278 7596:Bibcode 7588:Toxicon 7334:2696173 6993:3 April 6939:3491871 6897:6433782 6787:3491871 6735:2553730 6694:4322209 6653:3511964 6618:7791610 6577:1730582 6495:20 July 6404:2751003 6299:enzyme. 6101:4301090 5982:6615489 5746:2841876 5723:Bibcode 5696:9417034 5676:Bibcode 5668:Science 5626:2709379 5556:7791615 5505:Enzymes 5490:2246896 5470:Bibcode 5444:2077683 5380:9 April 5056:3 April 4916:2 April 4801:6016374 4713:20 July 4665:6436737 4642:Bibcode 4613:20 July 4528:1998683 4484:6379291 4324:5332569 4163:(DEL). 4005:choline 4001:acetate 3894:. Many 3747:of the 3741:aspirin 3697:legumes 3653:of the 3595:in the 3586:tubulin 3557:legumes 3537:barnase 3533:barstar 3523:trypsin 3479:glucose 3406:poisons 3392:group. 3331:in the 3262:, 1992. 3240:trypsin 3050:adducts 3030:alkenes 2705:value. 610:binding 465:compete 434:Cleland 279:serpins 150:poisons 134:balance 44:(S) to 10362:Lyases 9926:(EC 4) 9802:(EC 3) 9709:(EC 2) 9669:1.13 9626:(EC 1) 9480: 9470: 9429: 9421: 9384: 9361: 9353: 9312: 9302: 9263: 9228: 9193: 9143: 9135: 9092: 9069: 9059: 9051: 8995: 8960: 8952: 8917: 8853: 8843: 8790: 8761: 8736: 8713: 8705: 8670: 8662: 8652: 8613: 8603: 8564: 8556: 8521: 8513: 8478: 8468: 8435: 8425: 8386: 8378: 8331: 8300: 8290: 8251: 8204: 8196: 8157: 8116: 8108: 8073: 8038: 8030: 8012:Lancet 7995: 7985: 7942: 7932: 7876: 7846: 7811: 7801: 7781:Toxins 7760: 7750: 7730:Toxins 7707: 7676: 7649: 7614: 7571: 7563: 7528: 7520: 7452: 7417: 7380: 7355: 7332: 7285: 7244: 7221: 7213: 7176: 7137: 7096: 7069:3 June 7055: 7028: 6976: 6946: 6936: 6895: 6858: 6829: 6794: 6784: 6733: 6692: 6651: 6616: 6606: 6575: 6531: 6481: 6454: 6446: 6411: 6401: 6362: 6319: 6290: 6253: 6230: 6222: 6187:3 June 6173: 6143: 6108: 6098: 6059: 6024: 5989: 5979: 5937: 5902: 5894: 5859: 5822: 5796: 5788: 5753: 5743: 5694: 5624: 5591:319722 5589: 5554: 5544: 5511: 5488: 5442: 5407: 5368: 5326: 5286: 5246: 5221: 5196: 5160: 5133: 5125: 5082: 5044: 5015: 4982: 4954: 4871: 4846: 4808: 4798: 4754:7 June 4740: 4699: 4672: 4662: 4599: 4569: 4561: 4526: 4491: 4481: 4467:: 25. 4438: 4415: 4363: 4331: 4321: 4275: 4089:lipids 4055:, and 4031:, and 4015:, and 3866: 3802:, and 3800:asthma 3760:kinase 3625:tomato 3621:potato 3589:dimers 3337: 3066:serine 2860:PTC124 2023:. 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