488:
369:(TIM). He took advantage of its simplicity—interconverting a single substrate and a single product. Using the enediol intermediate of the reaction (which allowed solvent protons to enter the reaction from the middle instead of only from the substrate or product) and kinetic isotope effects, he measured the relative free energy of each intermediate and transition state, which allowed him to depict the first free energy profile for an enzyme-catalyzed reaction. This work was done with his long-term collaborator,
373:. His profile showed that TIM was a "perfect" enzyme in that catalysis is limited only by the rate of diffusion. Later, Knowles applied similar methods to proline racemase, developing an elegant method to discern whether a reaction proceeds via a stepwise or concerted manner and discovering the consequences of "oversaturation", a situation in which the interconversion of unliganded forms of the enzyme limit catalysis.
362:, which are nonspecific proteases, meaning they accept a broad range of substrates. He researched what made these enzymes nonspecific and how they increased the rate of peptide-bond hydrolysis. In 1972, Knowles developed a method for photo-affinity labelling, enabling the formation of a covalent bond between a protein and a ligand under the control of light.
255:
of the
Harvard University faculty of arts and sciences (FAS) from 1991 to 2002. He joined Harvard in 1974, received many awards for his research, and remained at Harvard until his death, leaving the faculty for a decade to serve as Dean. Knowles died on 3 April 2008 at his home.
376:
At
Harvard, Knowles also did important work on β-lactamases and their mechanism-based inhibitors. And, he provided key insight on the stereochemistry of phosphoryl group transfer reactions, using synthetic phosphoryl groups containing O, O, and O isotopes.
331:. Together, they found that some catalyzed reactions can occur up to one-million times faster than non-catalyzed reactions. Intrigued by this discovery, Knowles became an enzymologist. For a brief time, Knowles was a visiting professor at
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641:
Raines, Ronald T.; Knowles, Jeremy R. (1987). "Enzyme relaxation in the reaction catalyzed by triosephosphate isomerase: Detection and kinetic characterization of two unliganded forms of the enzyme".
1077:
Jones, Stephen R.; Kindman, L. Allen; Knowles, Jeremy R. (1978). "Stereochemistry of phosphoryl group transfer using a chiral [16O, 17O, 18O] stereochemical course of alkaline phosphatase".
1272:
307:'s physical organic chemistry laboratory. There, he studied electronic effects on the rates of aromatic substitution reactions. In 1960, he became a University Lecturer at Oxford, and Fellow of
495:
The Royal
Society of Chemistry awards a 'Jeremy Knowles Award', " to recognise and promote the importance of inter- and multi-disciplinary research between chemistry and the life sciences".
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Fisher, L. Mark; Albery, W. John; Knowles, Jeremy R. (1986). "Energetics of proline racemase: Racemization of unlabeled proline in the unsaturated, saturated, and oversaturated regimes".
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Addadi, Lia; Jaffe, Eileen K.; Knowles, Jeremy R. (1983). "Secondary tritium isotope effects as probes of the enzymic and nonenzymic conversion of chorismate to prephenate".
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Knowles was the author of more than 250 research papers, and advised many doctoral students and post-doctoral researchers at Oxford and at
Harvard, including
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Buchwald, Stephen L.; Knowles, Jeremy R. (1982). "Nucleophilic displacements on phosphoric monoesters: Stereochemical evidence".
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527:(1978). "Photogenerated reagents for membrane labeling. 2. Phenylcarbene and adamantylidene formed within the lipid bilayer".
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Knowles, J R; Norman, R O C; Radda, G K (1960). "A quantitative treatment of electrophilic aromatic substitution".
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to return to his position as Dean of the
Faculty of Arts and Sciences on an interim basis, replacing
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Albery, W. John; Knowles, Jeremy R. (1977). "Efficiency and
Evolution of Enzyme Catalysis".
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Knowles, Jeremy R. (1972). "Photogenerated reagents for biological receptor-site labeling".
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335:. in 1974, Knowles moved his research group to Harvard and became a professor there.
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Knowles married Jane
Sheldon Davis in 1960, and together they had three sons.
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806:, Harvard University Gazette, published 2006-05-22. Retrieved 2009-06-10.
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Jeremy R. Knowles named
Interim Dean of the Faculty of Arts and Sciences
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Repligen
Corporation Award in Chemistry of Biological Processes
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Repligen
Corporation Award in Chemistry of Biological Processes
359:
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247:(28 April 1935 – 3 April 2008) was a professor of chemistry at
171:
890:
102:
93:
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Knowles then began seminal studies on the glycolytic enzyme
491:
Royal Society of Chemistry – Jeremy Knowles Award (2014)
728:
Raines, R. T. (2008). "Jeremy R. Knowles (1935–2008)".
259:
In 2006, he was selected by incoming interim president
1546:
Foreign associates of the National Academy of Sciences
933:"Specificity and stereospecificity of α-chymotrypsin"
591:
426:
Foreign Associate of the National Academy of Sciences
1541:
Fellows of the American Academy of Arts and Sciences
452:
of the Royal Society, and was an Honorary Fellow of
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1041:
422:
American Association for the Advancement of Science
414:
Fellow of the American Academy of Arts and Sciences
319:In 1961, he took a post-doctoral fellowship at the
1551:People educated at Magdalen College School, Oxford
1009:Angewandte Chemie International Edition in English
675:
594:"The pH-dependence of pepsin-catalysed reactions"
354:function. Early in his career, Knowles studied α-
287:1958, first class degree in Chemistry 1959), and
275:Knowles was born in England in 1935, educated at
1512:
561:
303:. During his undergraduate he did research in
592:Cornish-Bowden, A. J.; Knowles, J. R. (1969).
1586:Members of the American Philosophical Society
1571:Commanders of the Order of the British Empire
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519:
480:. He was elected one of nine Trustees of the
765:(from the office of news and public affairs)
460:, Oxford. He held honorary degrees from the
346:, and concerned the rate and specificity of
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874:Intramolecular effects in aromatic systems
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338:Knowles's research was on the boundary of
178:Intramolecular effects in aromatic systems
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564:Journal of the American Chemical Society
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1154:American Academy of Arts & Sciences
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860:. Oxford: Basil Blackwell. p. 511.
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881:(DPhil thesis). University of Oxford.
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466:Eidgenössische Technische Hochschule
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1561:Fellows of Balliol College, Oxford
321:California Institute of Technology
165:California Institute of Technology
14:
1597:
1556:Alumni of Balliol College, Oxford
858:Merton College Register 1900-1964
1581:Alumni of Merton College, Oxford
931:Ingles, DW; Knowles, JR (1967).
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418:American Philosophical Society
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1536:Fellows of the Royal Society
856:Levens, R.G.C., ed. (1964).
442:Arthur C. Cope Scholar Award
270:
7:
474:Order of the British Empire
428:. Among his awards are the
410:Fellow of the Royal Society
220:Other notable students
16:British chemist (1935–2008)
10:
1602:
1566:Harvard University faculty
1248:Royal Society of Chemistry
1244:"RSC Jeremy Knowles Award"
817:"Harvard Gazette Obituary"
430:Royal Society of Chemistry
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367:triosephosphate isomerase
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1576:Royal Air Force officers
1230:23 November 2005 at the
1150:"Jeremy Randall Knowles"
871:Knowles, Jeremy (1961).
842:Daily Telegraph Obituary
712:"Jeremy Randall Knowles"
124:Welch Award in Chemistry
79:Cambridge, Massachusetts
1493:Wilfred A. van der Donk
786:Harvard Crimson Profile
462:University of Edinburgh
432:'s Charmian Medal, the
281:Balliol College, Oxford
90:Balliol College, Oxford
1021:10.1002/anie.197702851
492:
408:Knowles was elected a
309:Wadham College, Oxford
289:Merton College, Oxford
236:Jeremy Randall Knowles
99:Merton College, Oxford
46:Jeremy Randall Knowles
1469:David W. Christianson
490:
478:1993 Birthday Honours
448:. He was awarded the
350:and the evolution of
327:, who was an organic
1385:Christopher T. Walsh
1179:search.amphilsoc.org
1175:"APS Member History"
918:10.1039/jr9600004885
730:ACS Chemical Biology
390:Athel Cornish-Bowden
206:Athel Cornish-Bowden
1343:Frank H. Westheimer
1325:Stephen J. Benkovic
1200:"Jeremy R. Knowles"
1091:1978Natur.275..564J
1056:10.1021/bi00357a037
994:10.1021/ar50052a006
937:Biochemical Journal
802:17 May 2008 at the
690:10.1021/bi00288a022
655:10.1021/bi00396a024
598:Biochemical Journal
576:10.1021/ja00369a055
541:10.1021/bi00605a026
472:. He was appointed
386:Stephen L. Buchwald
315:Career and research
201:Stephen L. Buchwald
1439:Hung-Wen (Ben) Liu
1397:Rowena G. Matthews
1379:David S. Eisenberg
1361:W. Wallace Cleland
1331:Harold A. Scheraga
895:uk.bl.ethos.710173
493:
404:Awards and honours
249:Harvard University
161:Harvard University
1508:
1507:
1481:John S. Blanchard
1457:Richard Armstrong
1367:William P. Jencks
1355:Judith P. Klinman
1349:Jeremy R. Knowles
1337:William W. Parson
1204:www.nasonline.org
1085:(5680): 564–565.
949:10.1042/bj1040369
742:10.1021/cb800099n
684:(19): 4494–4501.
649:(22): 7014–7020.
610:10.1042/bj1130353
535:(12): 2420–2423.
394:Andreas PlĂĽckthun
325:George S. Hammond
233:
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189:Doctoral students
141:Scientific career
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1531:British chemists
1451:Ronald T. Raines
1433:Michael Marletta
1373:James A. Spudich
1319:Robert H. Abeles
1313:Thomas C. Bruice
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348:enzyme catalysis
295:1961). He was a
265:William C. Kirby
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434:Bader Award
371:John Albery
1515:Categories
879:jisc.ac.uk
521:Bayley, H.
507:References
450:Davy Medal
444:, and the
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271:Biography
261:Derek Bok
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