591:
644:
724:
multidrug resistance, exacerbated by incubation in immune-compromised AIDS victims, drug treatment non-compliance, and ongoing systemic deficiencies of healthcare in developing countries. Mortality and infection rates appear to have peaked, but TB remains a serious global problem. New effective drugs are needed to combat this disease. Inhibitors against mtFabH, or against other enzymes of the FAS-II pathway, may have broader utility, such as the treatment of multidrug-resistant
3152:
246:
636:= 77 ± 25 kDa. Although there is substantial structural homology among all bacterial FabH enzymes determined thus far, with two channels for binding of acyl-CoA and malonyl-ACP substrates and a conserved catalytic triad (C122, H258, N289 in mtFabH), mtFabH contains residues along the acyl-CoA binding channel that preferentially select for longer-chain substrates peaking with lauroyl-CoA (C
538:, evades effective immune clearance through encapsulation, especially with mycolic acids that are particularly resistant to the normal degradative processes of macrophages. Furthermore, this capsule inhibits entry of antibiotics. The enzymes involved in mycolate biosynthesis are essential for survival and pathogenesis, and thus represent excellent drug targets.
743:
Given the predominance of TB in poor countries, the commercial incentive to develop new drugs has been hampered, along with complacency and reliance on old, well-established, "first-line" drugs such as
Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol. The price point is already very low: US$ 16–35
1475:
Daines RA, Pendrak I, Sham K, Van Aller GS, Konstantinidis AK, Lonsdale JT, Janson CA, Qiu X, Brandt M, Khandekar SS, Silverman C, Head MS (January 2003). "First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor achieved using rational design and homology
723:
caused approximately 1.6 million deaths worldwide, 8.8 million people became sick, with 90% of these cases in developing countries, and an estimated one-third of the world's population has latent TB. Despite the availability of the BCG vaccine and multiple antibiotics, until 2005 TB resurged due to
628:
The catalytic activity and substrate specificity of mtFabH has been measured then further probed using crystallographic and directed mutagenesis methods. Structures have been determined of ecFabH bound with substrates, (CoA, malonyl CoA, degraded CoA). Specific inhibitors developed using rational
710:
It is speculated that novel inhibitors will most likely be small molecules of relatively low polarity, considering that the catalytic sites of the mtFabH homodimer are hidden in relatively hydrophobic pockets and the need to traverse capsules of established bacilli. This is supported by the poor
640:). Inhibition strategies based on rational design could include competitive displacement of the substrates or disruption of the catalytic site. Phosphorylation of Thr, which is located at the entrance of the substrate channel, inhibits activity, perhaps by altering accessibility of substrates.
711:
water solubility of an inhibitor to ecFabH. It is also hoped that, by being small molecules, their synthesis or biosynthesis will be simple and cheap, thereby enhancing affordability of subsequent drugs to developing countries. Techniques for screening efficacy of inhibitors are available.
581:
flux balance analyses, mtFabH is essential but not according to transposon site hybridization analysis. Unlike the enzymes in FAS-I, the enzymes of FAS-II, including mtFabH, and are not found in mammals, suggesting inhibitors of these enzymes are suitable choices for drug development.
1897:
Young K, Jayasuriya H, Ondeyka JG, Herath K, Zhang C, Kodali S, Galgoci A, Painter R, Brown-Driver V, Yamamoto R, Silver LL, Zheng Y, Ventura JI, Sigmund J, Ha S, Basilio A, Vicente F, Tormo JR, Pelaez F, Youngman P, Cully D, Barrett JF, Schmatz D, Singh SB, Wang J (February 2006).
1947:
Ondeyka JG, Zink DL, Young K, Painter R, Kodali S, Galgoci A, Collado J, Tormo JR, Basilio A, Vicente F, Wang J, Singh SB (March 2006). "Discovery of bacterial fatty acid synthase inhibitors from a Phoma species as antimicrobial agents using a new antisense-based strategy".
1511:
Nie Z, Perretta C, Lu J, Su Y, Margosiak S, Gajiwala KS, Cortez J, Nikulin V, Yager KM, Appelt K, Chu S (March 2005). "Structure-based design, synthesis, and study of potent inhibitors of beta-ketoacyl-acyl carrier protein synthase III as potential antimicrobial agents".
747:
According to the Global
Alliance for TB Drug Development, sales of first-line TB drugs are projected to be approximately US$ 315 million per year, and US$ 54 million for second-line treatments, yet the global economic toll of TB is at least $ 12 billion each year.
675:
While much has been learned from these structural studies and rational design is an excellent approach to develop novel inhibitors, alternative approaches such as bio-prospecting may reveal unexpected compounds such as an allosteric inhibitor discovered by Daines
1983:
Wang J, Kodali S, Lee SH, Galgoci A, Painter R, Dorso K, Racine F, Motyl M, Hernandez L, Tinney E, Colletti SL, Herath K, Cummings R, Salazar O, González I, Basilio A, Vicente F, Genilloud O, Pelaez F, Jayasuriya H, Young K, Cully DF, Singh SB (May 2007).
680:
This could be especially important given that phosphorylation of mycolate synthesis enzymes is suggested to be critical to regulation and kinase domains are known to have multiple control mechanisms remote from ligand binding and active sites.
702:
activity called platencin. These were found by screening 250,000 extracts of soil bacteria and fungi, demonstrating the viability of bio-prospecting. While a potentially useful antibiotic in its own right, it has now been shown that
1753:
Senior SJ, Illarionov PA, Gurcha SS, Campbell IB, Schaeffer ML, Minnikin DE, Besra GS (January 2004). "Acetylene-based analogues of thiolactomycin, active against
Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme".
1717:
Senior SJ, Illarionov PA, Gurcha SS, Campbell IB, Schaeffer ML, Minnikin DE, Besra GS (November 2003). "Biphenyl-based analogues of thiolactomycin, active against
Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme".
1592:
Musayev F, Sachdeva S, Scarsdale JN, Reynolds KA, Wright HT (March 2005). "Crystal structure of a substrate complex of
Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FabH) with lauroyl-coenzyme A".
452:. β-Ketoacyl-acyl-carrier-protein synthase III is involved in the dissociated (or type II) fatty-acid biosynthesis system that occurs in plants and bacteria. The role of FabH in fatty acid synthesis has been described in
671:
spp. Isoniazid (isonicotinic acid hydrazide), ethionamide, triclosan and TLM are known to specifically inhibit mycolic acid biosynthesis. Derivatives of TLM and related compounds are being screened to improve efficacy.
597:. The enzyme is a homodimer of mixed α-helices and β-sheets, or a thiolase fold. The catalytic triads of C122, H258, and N289 are shown in colour and are largely buried in hydrophobic pockets.
17:
405:
573:
fatty acid constitutes the alpha branch of the final mycolic acid. MtFabH has been proposed to be the link between FAS-I and FAS-II by converting C14-CoA generated by FAS-I to C
1426:"Probing the mechanism of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III mtFabH: factors influencing catalysis and substrate specificity"
1838:
Al-Balas Q, Anthony NG, Al-Jaidi B, Alnimr A, Abbott G, Brown AK, Taylor RC, Besra GS, McHugh TD, Gillespie SH, Johnston BF, Mackay SP, Coxon GD (2009). Todd MH (ed.).
200:
329:
2230:
2515:
961:"The Mycobacterium tuberculosis FAS-II condensing enzymes: their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development"
912:"Alteration of the Fatty Acid Profile of Streptomyces coelicolor by Replacement of the Initiation Enzyme 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)"
2752:
1682:
Schroeder EK, de Souza N, Santos DS, Blanchard JS, Basso LA (September 2002). "Drugs that inhibit mycolic acid biosynthesis in
Mycobacterium tuberculosis".
2349:
857:
Khandekar SS, Gentry DR, Van Aller GS, Warren P, Xiang H, Silverman C, Doyle ML, Chambers PA, Konstantinidis AK, Brandt M, Daines RA, Lonsdale JT (2001).
1141:
Qiu X, Janson CA, Smith WW, Head M, Lonsdale J, Konstantinidis AK (March 2001). "Refined structures of beta-ketoacyl-acyl carrier protein synthase III".
1547:
Ashek A, Cho SJ (March 2006). "A combined approach of docking and 3D QSAR study of beta-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors".
810:"Characterization of β-Ketoacyl-Acyl Carrier Protein Synthase III from Streptomyces glaucescens and Its Role in Initiation of Fatty Acid Biosynthesis"
1840:"Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH"
1633:"The Mycobacterium tuberculosis β-Ketoacyl-Acyl Carrier Protein Synthase III Activity Is Inhibited by Phosphorylation on a Single Threonine Residue"
2151:
He X, Mueller JP, Reynolds KA (June 2000). "Development of a scintillation proximity assay for beta-ketoacyl-acyl carrier protein synthase III".
219:
2688:
2683:
769:"The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli"
1369:"Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis"
1353:Inagaki E, Kuramitsu S, Yokoyama S, Miyano M, Tahirov TH (2007) The Crystal Structure of Beta-Ketoacyl- Synthase III (Fabh) from
2489:
2187:
2703:
1306:"Crystal structure of beta-ketoacyl-acyl carrier protein synthase III. A key condensing enzyme in bacterial fatty acid biosynthesis"
629:
design have recently been reported. In 2005, the structure of a catalytically disabled mtFabH mutant with lauroyl-CoA was reported.
2671:
1247:"Crystal structure and substrate specificity of the β-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus"
212:
2102:
Viader-Salvadó JM, Garza-González E, Valdez-Leal R, del Bosque-Moncayo MA, Tijerina-Menchaca R, Guerrero-Olazarán M (July 2001).
1304:
Qiu X, Janson CA, Konstantinidis AK, Nwagwu S, Silverman C, Smith WW, Khandekar S, Lonsdale J, Abdel-Meguid SS (December 1999).
2678:
2411:"Isolation and characterization of the beta-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12"
163:
349:
2666:
3177:
2838:
2331:
2255:
2806:
2234:
2871:
2622:
2560:
663:
At least two of the existing drugs for tuberculosis were originally derived from microbes; cerulenin from the fungus
2617:
2612:
30:
This article is about the specific variant of the enzyme type III. For the function and the enzyme in general, see
2555:
157:
2570:
2482:
1791:"1,2-Dithiole-3-Ones as Potent Inhibitors of the Bacterial 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)"
139:
1631:
Veyron-Churlet R, Molle V, Taylor RC, Brown AK, Besra GS, Zanella-Cléon I, Fütterer K, Kremer L (March 2009).
337:
144:
3027:
2735:
2715:
2629:
2381:
2656:
2550:
2545:
224:
2818:
2592:
390:
132:
3142:
2828:
2661:
2535:
603:
530:
333:
31:
250:
Structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from
3128:
3115:
3102:
3089:
3076:
3063:
3050:
3012:
2776:
2587:
2540:
2475:
1188:"Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III"
67:
1424:
Brown AK, Sridharan S, Kremer L, Lindenberg S, Dover LG, Sacchettini JC, Besra GS (September 2005).
160:
3022:
2976:
2919:
2781:
2506:
569:
acyl-CoA product acts as a substrate for the synthesis of meromycolic acid by FAS-II, whereas the C
458:
415:
366:
84:
50:
478:
of this enzyme class is acetyl-CoA:malonyl- C-acyltransferase. Other names in common use include:
2924:
2823:
2730:
2357:"New Study Reveals Limitations of a Complex and Challenging Global Tuberculosis Drug Marketplace"
449:
684:
Following the discovery that phomallenic acids isolated from a leaf litter fungus identified as
545:, the beta-ketoacyl- synthase III enzyme is designated mtFabH and is a crucial link between the
2791:
2786:
2651:
694:
2945:
2864:
2771:
2766:
2356:
1245:
Qiu X, Choudhry AE, Janson CA, Grooms M, Daines RA, Lonsdale JT, Khandekar SS (August 2005).
732:
726:
609:
120:
3017:
2833:
2720:
2707:
2607:
2056:
1997:
1986:"Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties"
1851:
1021:
621:
316:
2467:
2188:"The growing burden of tuberculosis: global trends and interactions with the HIV epidemic"
96:
8:
2981:
2565:
2101:
550:
546:
423:
62:
55:
2060:
2001:
1855:
1025:
590:
2914:
2308:
2281:
2079:
2044:
2020:
1985:
1924:
1899:
1874:
1839:
1659:
1632:
1271:
1246:
1217:
1098:
1044:
1009:
990:
936:
911:
892:
2427:
2410:
2186:
Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, Dye C (May 2003).
1815:
1790:
834:
809:
785:
768:
744:
will buy a full six-month drug course
Nevertheless, new drugs are in clinical trials.
3172:
2796:
2525:
2456:
2447:
2432:
2313:
2212:
2168:
2133:
2128:
2103:
2084:
2025:
1965:
1929:
1879:
1820:
1771:
1735:
1699:
1664:
1610:
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1564:
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1327:
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1235:
1209:
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1119:
1090:
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1049:
982:
977:
960:
941:
927:
884:
839:
825:
790:
381:
324:
151:
2119:
1806:
1221:
1102:
994:
896:
278:
175:
2960:
2955:
2929:
2857:
2761:
2725:
2422:
2303:
2293:
2202:
2160:
2123:
2115:
2074:
2064:
2015:
2005:
1957:
1919:
1911:
1869:
1859:
1810:
1802:
1763:
1727:
1691:
1654:
1644:
1602:
1556:
1521:
1485:
1437:
1380:
1317:
1266:
1258:
1199:
1150:
1080:
1039:
1029:
972:
931:
923:
874:
829:
821:
780:
615:
312:
1915:
1010:"Flux Balance Analysis of Mycolic Acid Pathway: Targets for Anti-Tubercular Drugs"
3007:
2991:
2904:
2801:
2502:
2298:
2069:
1864:
1034:
475:
442:
290:
2207:
3156:
3045:
2986:
1990:
Proceedings of the
National Academy of Sciences of the United States of America
1767:
1731:
431:
195:
2335:
1606:
1560:
643:
179:
3166:
2950:
2909:
2259:
1695:
1322:
1305:
1069:"Genes required for mycobacterial growth defined by high density mutagenesis"
704:
170:
2010:
2899:
2317:
2216:
2172:
2164:
2137:
2088:
2029:
1969:
1933:
1883:
1824:
1775:
1739:
1703:
1668:
1649:
1614:
1568:
1533:
1497:
1451:
1442:
1425:
1394:
1385:
1368:
1331:
1280:
1213:
1204:
1187:
1162:
1154:
1094:
1053:
986:
945:
888:
879:
858:
794:
720:
554:
535:
2436:
2043:
Brown AK, Taylor RC, Bhatt A, FĂĽtterer K, Besra GS (2009). Ahmed N (ed.).
843:
3123:
3058:
2894:
2740:
2498:
2104:"Mycolic Acid Index Susceptibility Method for Mycobacterium tuberculosis"
1262:
438:
369:
108:
2045:"Platensimycin Activity against Mycobacterial β-Ketoacyl-ACP Synthases"
427:
419:
362:
2248:
1961:
1586:
1525:
1489:
1469:
1418:
1412:
1349:
1298:
1239:
1180:
1135:
1129:
1123:
3097:
3071:
377:
1186:
Scarsdale JN, Kazanina G, He X, Reynolds KA, Wright HT (June 2001).
648:
Substrate specificity of mtFabH in relation to acyl-CoA chain length
3151:
2530:
285:
2324:
2282:"New Approaches to Filling the Gap in Tuberculosis Drug Discovery"
2461:
2451:
1789:
He X, Reeve AM, Desai UR, Kellogg GE, Reynolds KA (August 2004).
737:
127:
1681:
1591:
3110:
2880:
2811:
2639:
2634:
2575:
577:-AcpM, which is channelled into the FAS-II cycle. According to
373:
344:
245:
207:
103:
91:
79:
1752:
1716:
1630:
1423:
859:"Identification, substrate specificity, and inhibition of the
856:
3084:
2693:
2580:
1837:
1303:
959:
Bhatt A, Molle V, Besra GS, Jacobs WR, Kremer L (June 2007).
736:, the causative agent of another serious refractory problem,
2446:
Overview of all the structural information available in the
1896:
2597:
2497:
1185:
306:
273:
115:
2849:
2460:(Mycobacterium tuberculosis 3-oxoacyl- synthase 3) at the
1474:
692:
recently reported their discovery from the soil bacterium
2334:. Global Alliance for TB Drug Development. Archived from
2258:. Global Alliance for TB Drug Development. Archived from
1900:"Discovery of FabH/FabF Inhibitors from Natural Products"
2374:
2042:
2409:
Tsay JT, Oh W, Larson TJ, Jackowski S, Rock CO (1992).
1946:
1367:
Choi KH, Kremer L, Besra GS, Rock CO (September 2000).
1244:
1007:
863:
beta-ketoacyl-acyl carrier protein synthase III (FabH)"
2185:
3140:
2408:
2363:. Global Alliance for TB Drug Development. 2007-05-14
958:
393:
1982:
766:
1788:
1366:
601:Crystal structures of FabH have been reported from
2279:
1140:
1008:Raman K, Rajagopalan P, Chandra N (October 2005).
399:
2233:. World Health Organization. 2007. Archived from
2150:
1066:
909:
445:transferring groups other than aminoacyl groups.
18:Beta-ketoacyl-(acyl-carrier-protein) synthase III
3164:
2280:Casenghi M, Cole ST, Nathan CF (November 2007).
2387:. Global Alliance for TB Drug Development. 2001
1626:
1624:
1510:
807:
667:and thiolactomycin (TLM) from the actinomycete
1114:
1112:
767:Davies C, Heath RJ, White SW, Rock CO (2000).
762:
760:
513:β-Ketoacyl (acyl carrier protein) synthase III
40:β-ketoacyl-(acyl-carrier-protein) synthase III
2865:
2483:
1067:Sassetti CM, Boyd DH, Rubin EJ (April 2003).
516:β-Ketoacyl-acyl-carrier-protein synthase III.
489:3-Ketoacyl-acyl carrier protein synthase III,
2689:2-acylglycerol-3-phosphate O-acyltransferase
2684:1-acylglycerol-3-phosphate O-acyltransferase
2273:
2179:
2144:
2095:
2036:
1976:
1940:
1890:
1831:
1782:
1746:
1710:
1675:
1621:
1575:
1540:
1504:
1458:
1401:
1360:
1287:
1228:
507:β-Ketoacyl-acyl carrier protein synthase III
1169:
1109:
1060:
1001:
952:
757:
585:
2872:
2858:
2490:
2476:
698:of a novel natural inhibitor of FabH with
688:sp. are inhibitors of the FabH/FabF. Wang
244:
2426:
2307:
2297:
2206:
2127:
2078:
2068:
2019:
2009:
1923:
1873:
1863:
1814:
1658:
1648:
1441:
1384:
1321:
1270:
1203:
1084:
1043:
1033:
976:
935:
878:
833:
784:
557:. FAS-I is involved in the synthesis of C
1546:
714:
642:
589:
524:
437:. This enzyme belongs to the family of
14:
3165:
2679:Glycerol-3-phosphate O-acyltransferase
2382:"The Economics of TB Drug Development"
2223:
707:is not specifically active on mtFabH.
650:. The optimum length is lauroyl-CoA, C
2853:
2672:Lecithin—cholesterol acyltransferase
2471:
2256:"TB Alliance — An Outdated Treatment"
910:Li Y, Florova G, Reynolds KA (2005).
2667:Glyceronephosphate O-acyltransferase
2361:TB Alliance Newscenter: News Release
2839:Sulfoacetaldehyde acetyltransferase
2531:Acetyl-Coenzyme A acetyltransferase
808:Han L, Lobo S, Reynolds KA (1998).
632:Native mtFabH is a homodimer with M
400:{\displaystyle \rightleftharpoons }
24:
2755:: converted into alkyl on transfer
2401:
2231:"Global Tuberculosis Control 2007"
25:
3189:
2561:Chloramphenicol acetyltransferase
2332:"TB Alliance — TB Drug Portfolio"
3150:
2613:Carnitine O-palmitoyltransferase
1086:10.1046/j.1365-2958.2003.03425.x
978:10.1111/j.1365-2958.2007.05761.x
928:10.1128/JB.187.11.3795-3799.2005
826:10.1128/JB.180.17.4481-4486.1998
2556:Beta-galactoside transacetylase
2120:10.1128/JCM.39.7.2642-2645.2001
1807:10.1128/AAC.48.8.3093-3102.2004
1338:
469:
2571:Serotonin N-acetyl transferase
2518:: other than amino-acyl groups
903:
850:
801:
394:
365:, a β-ketoacyl- synthase III (
13:
1:
2736:Keratinocyte transglutaminase
2716:Gamma-glutamyl transpeptidase
2630:Serine C-palmitoyltransferase
2428:10.1016/S0021-9258(19)50498-7
1916:10.1128/AAC.50.2.519-526.2006
786:10.1016/S0969-2126(00)00094-0
751:
658:
301:Available protein structures:
2657:Aminolevulinic acid synthase
2551:Acetyl-CoA C-acyltransferase
2546:Dihydrolipoyl transacetylase
2299:10.1371/journal.pmed.0040293
2070:10.1371/journal.pone.0006306
1904:Antimicrob. Agents Chemother
1865:10.1371/journal.pone.0005617
1795:Antimicrob. Agents Chemother
1035:10.1371/journal.pcbi.0010046
448:This enzyme participates in
422:and malonyl-, whereas its 3
7:
2879:
2819:2-hydroxyglutarate synthase
2208:10.1001/archinte.163.9.1009
510:β-Ketoacyl-ACP synthase III
10:
3194:
3178:Enzymes of known structure
2829:2-isopropylmalate synthase
2662:Beta-ketoacyl-ACP synthase
2536:N-Acetylglutamate synthase
1768:10.1016/j.bmcl.2003.10.061
1732:10.1016/j.bmcl.2003.08.015
604:Mycobacterium tuberculosis
531:Mycobacterium tuberculosis
486:3-Oxoacyl:ACP synthase III
32:Beta-ketoacyl-ACP synthase
29:
3036:
3028:Michaelis–Menten kinetics
3000:
2969:
2938:
2887:
2777:Decylhomocitrate synthase
2751:
2702:
2588:Histone acetyltransferase
2541:Choline acetyltransferase
2514:
1607:10.1016/j.jmb.2004.12.044
1561:10.1016/j.bmc.2005.10.001
343:
323:
305:
300:
296:
284:
272:
264:
259:
243:
238:
218:
206:
194:
189:
185:
169:
150:
138:
126:
114:
102:
90:
78:
73:
61:
49:
44:
39:
2920:Diffusion-limited enzyme
2782:2-methylcitrate synthase
1696:10.2174/1389201023378328
1323:10.1074/jbc.274.51.36465
861:Streptococcus pneumoniae
665:Cephalosporium caerulens
586:Structure and substrates
459:Streptococcus pneumoniae
454:Streptomyces glaucescens
2824:3-propylmalate synthase
2731:Tissue transglutaminase
2011:10.1073/pnas.0700746104
1756:Bioorg. Med. Chem. Lett
1720:Bioorg. Med. Chem. Lett
595:The structure of mtFabH
553:-II pathways producing
464:Streptomyces coelicolor
450:fatty acid biosynthesis
441:, to be specific those
407:acetoacetyl- + CoA + CO
239:3-Oxoacyl- synthase III
2792:3-ethylmalate synthase
2787:2-ethylmalate synthase
2652:Acyltransferase like 2
2165:10.1006/abio.2000.4594
1650:10.1074/jbc.M806537200
1443:10.1074/jbc.M413216200
1386:10.1074/jbc.M003241200
1205:10.1074/jbc.M010762200
1155:10.1006/jmbi.2000.4457
880:10.1074/jbc.M101769200
695:Streptomyces platensis
655:
598:
401:
387:acetyl-CoA + malonyl-
3013:Eadie–Hofstee diagram
2946:Allosteric regulation
2772:Citrate (Re)-synthase
2767:Decylcitrate synthase
2708:Aminoacyltransferases
2608:palmitoyltransferases
1684:Curr Pharm Biotechnol
733:Plasmodium falciparum
727:Staphylococcus aureus
715:Therapeutic potential
646:
610:Staphylococcus aureus
593:
402:
3023:Lineweaver–Burk plot
2834:Homocitrate synthase
2721:Peptidyl transferase
1355:Thermus thermophilus
1263:10.1110/ps.051501605
622:Thermus thermophilus
525:Role in tuberculosis
391:
2566:N-acetyltransferase
2061:2009PLoSO...4.6306B
2002:2007PNAS..104.7612W
1856:2009PLoSO...4.5617A
1026:2005PLSCB...1...46R
551:fatty acid synthase
547:fatty acid synthase
418:of this enzyme are
2982:Enzyme superfamily
2915:Enzyme promiscuity
2526:acetyltransferases
2108:J. Clin. Microbiol
656:
599:
565:fatty acids. The C
426:are acetoacetyl-,
397:
3138:
3137:
2847:
2846:
2797:ATP citrate lyase
2195:Arch. Intern. Med
1962:10.1021/np050416w
1549:Bioorg. Med. Chem
1526:10.1021/jm049141s
1490:10.1021/jm025571b
1014:PLOS Comput. Biol
522:
521:
382:chemical reaction
359:
358:
355:
354:
350:structure summary
234:
233:
230:
229:
133:metabolic pathway
16:(Redirected from
3185:
3155:
3154:
3146:
3018:Hanes–Woolf plot
2961:Enzyme activator
2956:Enzyme inhibitor
2930:Enzyme catalysis
2874:
2867:
2860:
2851:
2850:
2807:HMG-CoA synthase
2762:Citrate synthase
2726:Transglutaminase
2503:acyltransferases
2492:
2485:
2478:
2469:
2468:
2440:
2430:
2396:
2395:
2393:
2392:
2386:
2378:
2372:
2371:
2369:
2368:
2353:
2347:
2346:
2344:
2343:
2328:
2322:
2321:
2311:
2301:
2277:
2271:
2270:
2268:
2267:
2252:
2246:
2245:
2243:
2242:
2227:
2221:
2220:
2210:
2192:
2183:
2177:
2176:
2148:
2142:
2141:
2131:
2099:
2093:
2092:
2082:
2072:
2040:
2034:
2033:
2023:
2013:
1980:
1974:
1973:
1944:
1938:
1937:
1927:
1894:
1888:
1887:
1877:
1867:
1835:
1829:
1828:
1818:
1786:
1780:
1779:
1750:
1744:
1743:
1714:
1708:
1707:
1679:
1673:
1672:
1662:
1652:
1628:
1619:
1618:
1589:
1579:
1573:
1572:
1544:
1538:
1537:
1508:
1502:
1501:
1472:
1462:
1456:
1455:
1445:
1436:(37): 32539–47.
1421:
1415:
1405:
1399:
1398:
1388:
1364:
1358:
1352:
1342:
1336:
1335:
1325:
1316:(51): 36465–71.
1301:
1291:
1285:
1284:
1274:
1242:
1232:
1226:
1225:
1207:
1198:(23): 20516–22.
1183:
1173:
1167:
1166:
1138:
1132:
1126:
1116:
1107:
1106:
1088:
1064:
1058:
1057:
1047:
1037:
1005:
999:
998:
980:
956:
950:
949:
939:
907:
901:
900:
882:
873:(32): 30024–30.
854:
848:
847:
837:
805:
799:
798:
788:
764:
616:Escherichia coli
481:
480:
443:acyltransferases
406:
404:
403:
398:
298:
297:
252:escherichia coli
248:
236:
235:
187:
186:
37:
36:
21:
3193:
3192:
3188:
3187:
3186:
3184:
3183:
3182:
3163:
3162:
3161:
3149:
3141:
3139:
3134:
3046:Oxidoreductases
3032:
3008:Enzyme kinetics
2996:
2992:List of enzymes
2965:
2934:
2905:Catalytic triad
2883:
2878:
2848:
2843:
2802:Malate synthase
2747:
2698:
2510:
2496:
2443:
2421:(10): 6807–14.
2404:
2402:Further reading
2399:
2390:
2388:
2384:
2380:
2379:
2375:
2366:
2364:
2355:
2354:
2350:
2341:
2339:
2330:
2329:
2325:
2278:
2274:
2265:
2263:
2254:
2253:
2249:
2240:
2238:
2229:
2228:
2224:
2190:
2184:
2180:
2149:
2145:
2100:
2096:
2041:
2037:
1981:
1977:
1945:
1941:
1895:
1891:
1836:
1832:
1801:(8): 3093–102.
1787:
1783:
1751:
1747:
1715:
1711:
1680:
1676:
1643:(10): 6414–24.
1629:
1622:
1581:
1580:
1576:
1545:
1541:
1520:(5): 1596–609.
1509:
1505:
1464:
1463:
1459:
1417:
1407:
1406:
1402:
1379:(36): 28201–7.
1365:
1361:
1344:
1343:
1339:
1293:
1292:
1288:
1234:
1233:
1229:
1175:
1174:
1170:
1134:
1128:
1118:
1117:
1110:
1065:
1061:
1006:
1002:
957:
953:
908:
904:
855:
851:
806:
802:
765:
758:
754:
717:
661:
653:
639:
635:
588:
576:
572:
568:
564:
560:
543:M. tuberculosis
534:, the cause of
527:
476:systematic name
472:
435:
410:
392:
389:
388:
255:
35:
28:
23:
22:
15:
12:
11:
5:
3191:
3181:
3180:
3175:
3160:
3159:
3136:
3135:
3133:
3132:
3119:
3106:
3093:
3080:
3067:
3054:
3040:
3038:
3034:
3033:
3031:
3030:
3025:
3020:
3015:
3010:
3004:
3002:
2998:
2997:
2995:
2994:
2989:
2984:
2979:
2973:
2971:
2970:Classification
2967:
2966:
2964:
2963:
2958:
2953:
2948:
2942:
2940:
2936:
2935:
2933:
2932:
2927:
2922:
2917:
2912:
2907:
2902:
2897:
2891:
2889:
2885:
2884:
2877:
2876:
2869:
2862:
2854:
2845:
2844:
2842:
2841:
2836:
2831:
2826:
2821:
2816:
2815:
2814:
2804:
2799:
2794:
2789:
2784:
2779:
2774:
2769:
2764:
2758:
2756:
2749:
2748:
2746:
2745:
2744:
2743:
2738:
2733:
2723:
2718:
2712:
2710:
2700:
2699:
2697:
2696:
2691:
2686:
2681:
2675:
2674:
2669:
2664:
2659:
2654:
2645:
2644:
2643:
2642:
2637:
2627:
2626:
2625:
2620:
2603:
2602:
2601:
2600:
2595:
2585:
2584:
2583:
2578:
2573:
2563:
2558:
2553:
2548:
2543:
2538:
2533:
2521:
2519:
2512:
2511:
2495:
2494:
2487:
2480:
2472:
2466:
2465:
2442:
2441:
2405:
2403:
2400:
2398:
2397:
2373:
2348:
2323:
2272:
2247:
2222:
2201:(9): 1009–21.
2178:
2143:
2094:
2035:
1996:(18): 7612–6.
1975:
1939:
1889:
1830:
1781:
1745:
1726:(21): 3685–8.
1709:
1690:(3): 197–225.
1674:
1620:
1601:(5): 1313–21.
1574:
1555:(5): 1474–82.
1539:
1503:
1457:
1400:
1359:
1337:
1286:
1257:(8): 2087–94.
1227:
1168:
1108:
1073:Mol. Microbiol
1059:
1000:
971:(6): 1442–54.
965:Mol. Microbiol
951:
922:(11): 3795–9.
902:
849:
820:(17): 4481–6.
800:
755:
753:
750:
716:
713:
660:
657:
651:
637:
633:
587:
584:
574:
570:
566:
562:
558:
526:
523:
520:
519:
518:
517:
514:
511:
508:
503:
502:
501:
496:
493:
490:
487:
471:
468:
433:
414:Thus, the two
412:
411:
408:
396:
357:
356:
353:
352:
347:
341:
340:
327:
321:
320:
310:
303:
302:
294:
293:
288:
282:
281:
276:
270:
269:
266:
262:
261:
257:
256:
249:
241:
240:
232:
231:
228:
227:
222:
216:
215:
210:
204:
203:
198:
192:
191:
183:
182:
173:
167:
166:
155:
148:
147:
142:
136:
135:
130:
124:
123:
118:
112:
111:
106:
100:
99:
94:
88:
87:
82:
76:
75:
71:
70:
65:
59:
58:
53:
47:
46:
42:
41:
26:
9:
6:
4:
3:
2:
3190:
3179:
3176:
3174:
3171:
3170:
3168:
3158:
3153:
3148:
3147:
3144:
3130:
3126:
3125:
3120:
3117:
3113:
3112:
3107:
3104:
3100:
3099:
3094:
3091:
3087:
3086:
3081:
3078:
3074:
3073:
3068:
3065:
3061:
3060:
3055:
3052:
3048:
3047:
3042:
3041:
3039:
3035:
3029:
3026:
3024:
3021:
3019:
3016:
3014:
3011:
3009:
3006:
3005:
3003:
2999:
2993:
2990:
2988:
2987:Enzyme family
2985:
2983:
2980:
2978:
2975:
2974:
2972:
2968:
2962:
2959:
2957:
2954:
2952:
2951:Cooperativity
2949:
2947:
2944:
2943:
2941:
2937:
2931:
2928:
2926:
2923:
2921:
2918:
2916:
2913:
2911:
2910:Oxyanion hole
2908:
2906:
2903:
2901:
2898:
2896:
2893:
2892:
2890:
2886:
2882:
2875:
2870:
2868:
2863:
2861:
2856:
2855:
2852:
2840:
2837:
2835:
2832:
2830:
2827:
2825:
2822:
2820:
2817:
2813:
2810:
2809:
2808:
2805:
2803:
2800:
2798:
2795:
2793:
2790:
2788:
2785:
2783:
2780:
2778:
2775:
2773:
2770:
2768:
2765:
2763:
2760:
2759:
2757:
2754:
2750:
2742:
2739:
2737:
2734:
2732:
2729:
2728:
2727:
2724:
2722:
2719:
2717:
2714:
2713:
2711:
2709:
2705:
2701:
2695:
2692:
2690:
2687:
2685:
2682:
2680:
2677:
2676:
2673:
2670:
2668:
2665:
2663:
2660:
2658:
2655:
2653:
2650:
2647:
2646:
2641:
2638:
2636:
2633:
2632:
2631:
2628:
2624:
2621:
2619:
2616:
2615:
2614:
2611:
2609:
2605:
2604:
2599:
2596:
2594:
2591:
2590:
2589:
2586:
2582:
2579:
2577:
2574:
2572:
2569:
2568:
2567:
2564:
2562:
2559:
2557:
2554:
2552:
2549:
2547:
2544:
2542:
2539:
2537:
2534:
2532:
2529:
2527:
2523:
2522:
2520:
2517:
2513:
2508:
2504:
2500:
2493:
2488:
2486:
2481:
2479:
2474:
2473:
2470:
2463:
2459:
2458:
2453:
2449:
2445:
2444:
2438:
2434:
2429:
2424:
2420:
2416:
2415:J. Biol. Chem
2412:
2407:
2406:
2383:
2377:
2362:
2358:
2352:
2338:on 2010-01-13
2337:
2333:
2327:
2319:
2315:
2310:
2305:
2300:
2295:
2291:
2287:
2283:
2276:
2262:on 2010-01-13
2261:
2257:
2251:
2237:on 2010-02-02
2236:
2232:
2226:
2218:
2214:
2209:
2204:
2200:
2196:
2189:
2182:
2174:
2170:
2166:
2162:
2159:(1): 107–14.
2158:
2154:
2153:Anal. Biochem
2147:
2139:
2135:
2130:
2125:
2121:
2117:
2114:(7): 2642–5.
2113:
2109:
2105:
2098:
2090:
2086:
2081:
2076:
2071:
2066:
2062:
2058:
2054:
2050:
2046:
2039:
2031:
2027:
2022:
2017:
2012:
2007:
2003:
1999:
1995:
1991:
1987:
1979:
1971:
1967:
1963:
1959:
1956:(3): 377–80.
1955:
1951:
1943:
1935:
1931:
1926:
1921:
1917:
1913:
1910:(2): 519–26.
1909:
1905:
1901:
1893:
1885:
1881:
1876:
1871:
1866:
1861:
1857:
1853:
1849:
1845:
1841:
1834:
1826:
1822:
1817:
1812:
1808:
1804:
1800:
1796:
1792:
1785:
1777:
1773:
1769:
1765:
1761:
1757:
1749:
1741:
1737:
1733:
1729:
1725:
1721:
1713:
1705:
1701:
1697:
1693:
1689:
1685:
1678:
1670:
1666:
1661:
1656:
1651:
1646:
1642:
1638:
1637:J. Biol. Chem
1634:
1627:
1625:
1616:
1612:
1608:
1604:
1600:
1596:
1588:
1584:
1578:
1570:
1566:
1562:
1558:
1554:
1550:
1543:
1535:
1531:
1527:
1523:
1519:
1515:
1507:
1499:
1495:
1491:
1487:
1483:
1479:
1471:
1467:
1461:
1453:
1449:
1444:
1439:
1435:
1431:
1430:J. Biol. Chem
1427:
1420:
1414:
1410:
1404:
1396:
1392:
1387:
1382:
1378:
1374:
1373:J. Biol. Chem
1370:
1363:
1356:
1351:
1347:
1341:
1333:
1329:
1324:
1319:
1315:
1311:
1310:J. Biol. Chem
1307:
1300:
1296:
1290:
1282:
1278:
1273:
1268:
1264:
1260:
1256:
1252:
1248:
1241:
1237:
1231:
1223:
1219:
1215:
1211:
1206:
1201:
1197:
1193:
1192:J. Biol. Chem
1189:
1182:
1178:
1172:
1164:
1160:
1156:
1152:
1149:(1): 341–56.
1148:
1144:
1137:
1131:
1125:
1121:
1115:
1113:
1104:
1100:
1096:
1092:
1087:
1082:
1078:
1074:
1070:
1063:
1055:
1051:
1046:
1041:
1036:
1031:
1027:
1023:
1019:
1015:
1011:
1004:
996:
992:
988:
984:
979:
974:
970:
966:
962:
955:
947:
943:
938:
933:
929:
925:
921:
917:
913:
906:
898:
894:
890:
886:
881:
876:
872:
868:
867:J. Biol. Chem
864:
862:
853:
845:
841:
836:
831:
827:
823:
819:
815:
811:
804:
796:
792:
787:
782:
779:(2): 185–95.
778:
774:
770:
763:
761:
756:
749:
745:
741:
739:
735:
734:
729:
728:
722:
712:
708:
706:
705:platensimycin
701:
697:
696:
691:
687:
682:
679:
673:
670:
666:
649:
645:
641:
630:
626:
624:
623:
618:
617:
612:
611:
606:
605:
596:
592:
583:
580:
556:
555:mycolic acids
552:
548:
544:
539:
537:
533:
532:
515:
512:
509:
506:
505:
504:
500:
497:
494:
491:
488:
485:
484:
483:
482:
479:
477:
467:
465:
461:
460:
455:
451:
446:
444:
440:
436:
429:
425:
421:
417:
386:
385:
384:
383:
379:
375:
371:
368:
364:
351:
348:
346:
342:
339:
335:
331:
328:
326:
322:
318:
314:
311:
308:
304:
299:
295:
292:
289:
287:
283:
280:
277:
275:
271:
267:
263:
258:
253:
247:
242:
237:
226:
223:
221:
217:
214:
211:
209:
205:
202:
199:
197:
193:
188:
184:
181:
177:
174:
172:
171:Gene Ontology
168:
165:
162:
159:
156:
153:
149:
146:
143:
141:
137:
134:
131:
129:
125:
122:
119:
117:
113:
110:
109:NiceZyme view
107:
105:
101:
98:
95:
93:
89:
86:
83:
81:
77:
72:
69:
66:
64:
60:
57:
54:
52:
48:
43:
38:
33:
19:
3124:Translocases
3121:
3108:
3095:
3082:
3069:
3059:Transferases
3056:
3043:
2900:Binding site
2648:
2606:
2524:
2499:Transferases
2455:
2418:
2414:
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2895:Active site
2741:Factor XIII
1476:modeling".
1251:Protein Sci
268:ACP_syn_III
260:Identifiers
85:IntEnz view
45:Identifiers
3167:Categories
3098:Isomerases
3072:Hydrolases
2939:Regulation
2391:2010-01-02
2367:2010-01-02
2342:2010-01-02
2266:2010-01-02
2241:2010-01-02
1484:(1): 5–8.
1020:(5): e46.
752:References
659:Inhibitors
420:acetyl-CoA
416:substrates
363:enzymology
313:structures
154:structures
121:KEGG entry
68:9077-10-5
2977:EC number
1590:;
1473:;
1422:;
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1184:;
1139:;
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1127:,
773:Structure
719:In 2005,
579:in silico
395:⇌
378:catalyzes
370:2.3.1.180
291:IPR013751
74:Databases
56:2.3.1.180
3173:EC 2.3.1
3001:Kinetics
2925:Cofactor
2888:Activity
2593:P300/CBP
2318:17988169
2286:PLOS Med
2217:12742798
2173:10860506
2138:11427584
2089:19609444
2049:PLOS ONE
2030:17456595
1970:16562839
1934:16436705
1884:19440303
1844:PLOS ONE
1825:15273125
1776:14698162
1740:14552758
1704:12164478
1669:19074144
1615:15713483
1569:16275103
1534:15743201
1498:12502353
1452:16040614
1395:10840036
1332:10593943
1281:15987898
1222:21814082
1214:11278743
1163:11243824
1103:21383026
1095:12657046
1054:16261191
995:32586686
987:17555433
946:15901703
897:40184365
889:11375394
795:10673437
669:Nocardia
424:products
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330:RCSB PDB
286:InterPro
225:proteins
213:articles
201:articles
158:RCSB PDB
3157:Biology
3111:Ligases
2881:Enzymes
2462:PDBe-KB
2452:UniProt
2437:1551888
2309:2062479
2080:2707616
2057:Bibcode
2021:1863502
1998:Bibcode
1925:1366929
1875:2680598
1852:Bibcode
1660:2649087
1272:2279320
1045:1246807
1022:Bibcode
937:1112031
844:9721286
738:malaria
700:in vivo
549:-I and
495:KAS III
279:PF08545
180:QuickGO
145:profile
128:MetaCyc
63:CAS no.
3143:Portal
3085:Lyases
2812:HMGCS2
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2640:SPTLC2
2635:SPTLC1
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678:et al.
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492:KASIII
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430:, and
374:enzyme
345:PDBsum
319:
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265:Symbol
208:PubMed
190:Search
176:AmiGO
164:PDBsum
104:ExPASy
92:BRENDA
80:IntEnz
51:EC no.
27:Enzyme
3037:Types
2753:2.3.3
2704:2.3.2
2694:ABHD5
2581:ARD1A
2516:2.3.1
2385:(PDF)
2191:(PDF)
2129:88200
1218:S2CID
1099:S2CID
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893:S2CID
686:Phoma
561:and C
376:that
140:PRIAM
3129:list
3122:EC7
3116:list
3109:EC6
3103:list
3096:EC5
3090:list
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3077:list
3070:EC3
3064:list
3057:EC2
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3044:EC1
2623:CPT2
2618:CPT1
2598:NAT2
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2433:PMID
2314:PMID
2213:PMID
2169:PMID
2134:PMID
2085:PMID
2026:PMID
1966:PMID
1930:PMID
1880:PMID
1821:PMID
1772:PMID
1736:PMID
1700:PMID
1665:PMID
1611:PMID
1587:1U6S
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1530:PMID
1494:PMID
1470:1MZS
1448:PMID
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1350:1UB7
1328:PMID
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1240:1ZOW
1210:PMID
1181:1HZP
1159:PMID
1136:1HNJ
1130:1HNH
1124:1HND
1091:PMID
1050:PMID
983:PMID
942:PMID
885:PMID
840:PMID
791:PMID
499:FabH
474:The
380:the
338:PDBj
334:PDBe
317:ECOD
307:Pfam
274:Pfam
220:NCBI
161:PDBe
116:KEGG
2448:PDB
2423:doi
2419:267
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2294:doi
2203:doi
2199:163
2161:doi
2157:282
2124:PMC
2116:doi
2075:PMC
2065:doi
2016:PMC
2006:doi
1994:104
1958:doi
1920:PMC
1912:doi
1870:PMC
1860:doi
1811:PMC
1803:doi
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1655:PMC
1645:doi
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