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Jeremy R. Knowles

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Jeremy Knowles
CBE FRS
Born
Jeremy Randall Knowles

(1935-04-28)28 April 1935
Rugby, England[6]
Died3 April 2008(2008-04-03) (aged 72)
Cambridge, Massachusetts[7]
EducationBalliol College, Oxford (BA)
Merton College, Oxford (DPhil)
Known forEnzyme catalysis
AwardsWelch Award in Chemistry (1995)
Nakanishi Prize (1999)
Scientific career
FieldsBiochemistry
InstitutionsHarvard University
California Institute of Technology
ThesisIntramolecular effects in aromatic systems (1961)
Doctoral students
Other notable studentsLia Addadi[5]

Jeremy Randall Knowles CBE FRS (28 April 1935 – 3 April 2008) was a professor of chemistry at Harvard University who served as dean of the Harvard University faculty of arts and sciences (FAS) from 1991 to 2002.[8][9][10] 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.[7]

In 2006, he was selected by incoming interim president Derek Bok to return to his position as Dean of the Faculty of Arts and Sciences on an interim basis, replacing William C. Kirby.[11][12][13]

Biography

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Knowles was born in England in 1935, educated at Magdalen College School, Oxford, Balliol College, Oxford (BA 1958, first class degree in Chemistry 1959), and Merton College, Oxford (DPhil 1961).[14][15] He was a Pilot Officer in the Royal Air Force. During his undergraduate he did research in Richard Norman's physical organic chemistry laboratory. There, he studied electronic effects on the rates of aromatic substitution reactions.[16] In 1960, he became a University Lecturer at Oxford, and Fellow of Wadham College, Oxford.

Career and research

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In 1961, he took a post-doctoral fellowship at the California Institute of Technology, working with George S. Hammond, who was an organic photo-chemist. 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 Yale University. in 1974, Knowles moved his research group to Harvard and became a professor there.

Knowles's research was on the boundary of chemistry and biochemistry, and concerned the rate and specificity of enzyme catalysis and the evolution of enzyme function. Early in his career, Knowles studied α-chymotrypsin[17] and pepsin,[3] 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.[18]

Knowles then began seminal studies on the glycolytic enzyme triosephosphate isomerase (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, John Albery.[19] 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,[20] 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.

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 16O, 17O, and 18O isotopes.[21]

Knowles was the author of more than 250 research papers, and advised many doctoral students and post-doctoral researchers[22] at Oxford and at Harvard, including Hagan Bayley, Stephen L. Buchwald, Athel Cornish-Bowden, Andreas Plückthun, and Ronald T. Raines.

Awards and honours

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Knowles was elected a Fellow of the Royal Society (FRS),[when?] a Fellow of the American Academy of Arts and Sciences (FAAAS) in 1982,[23] and member of American Philosophical Society in 1988,[24] the American Association for the Advancement of Science, and a Foreign Associate of the National Academy of Sciences.[25] Among his awards are the Royal Society of Chemistry's Charmian Medal, the Bader Award, the Repligen Corporation Award in Chemistry of Biological Processes, the Prelog Medal, the Robert A. Welch Award in Chemistry, the Arthur C. Cope Scholar Award, and the Nakanishi Prize. He was awarded the Davy Medal of the Royal Society, and was an Honorary Fellow of Balliol College and of Wadham College, Oxford. He held honorary degrees from the University of Edinburgh and the Eidgenössische Technische Hochschule in Zürich. He was appointed Order of the British Empire in the 1993 Birthday Honours. He was elected one of nine Trustees of the Howard Hughes Medical Institute in 1998.[26]

Royal Society of Chemistry – Jeremy Knowles Award (2014)

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".[27]

Personal life

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Knowles married Jane Sheldon Davis in 1960, and together they had three sons.[14]

References

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  1. ^ Bayley, H.; Knowles, J. R. (1978). "Photogenerated reagents for membrane labeling. 2. Phenylcarbene and adamantylidene formed within the lipid bilayer". Biochemistry. 17 (12): 2420–2423. doi:10.1021/bi00605a026. PMID 678520.
  2. ^ Buchwald, Stephen L.; Knowles, Jeremy R. (1982). "Nucleophilic displacements on phosphoric monoesters: Stereochemical evidence". Journal of the American Chemical Society. 104 (5): 1438–1440. doi:10.1021/ja00369a055.
  3. ^ a b Cornish-Bowden, A. J.; Knowles, J. R. (1969). "The pH-dependence of pepsin-catalysed reactions". Biochemical Journal. 113 (2): 353–362. doi:10.1042/bj1130353. PMC 1184642. PMID 4897198.
  4. ^ 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". Biochemistry. 26 (22): 7014–7020. doi:10.1021/bi00396a024. PMID 3427057.
  5. ^ 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". Biochemistry. 22 (19): 4494–4501. doi:10.1021/bi00288a022. PMID 6354259.
  6. ^ "Jeremy Randall Knowles". 14 May 2009.
  7. ^ a b Raines, R. T. (2008). "Jeremy R. Knowles (1935–2008)". ACS Chemical Biology. 3 (5): 262–264. doi:10.1021/cb800099n. PMID 18484705.
  8. ^ Bio from Harvard (from the office of news and public affairs)
  9. ^ "Public biography". Archived from the original on 30 December 2004. Retrieved 20 December 2005.
  10. ^ Harvard Crimson Profile
  11. ^ Jeremy R. Knowles named Interim Dean of the Faculty of Arts and Sciences Archived 17 May 2008 at the Wayback Machine, Harvard University Gazette, published 2006-05-22. Retrieved 2009-06-10.
  12. ^ "Harvard Gazette Obituary". Archived from the original on 11 May 2008. Retrieved 4 April 2008.
  13. ^ Daily Telegraph Obituary
  14. ^ a b Levens, R.G.C., ed. (1964). Merton College Register 1900-1964. Oxford: Basil Blackwell. p. 511.
  15. ^ Knowles, Jeremy (1961). Intramolecular effects in aromatic systems. jisc.ac.uk (DPhil thesis). University of Oxford. OCLC 275990698. EThOS uk.bl.ethos.710173.[permanent dead link]
  16. ^ Knowles, J R; Norman, R O C; Radda, G K (1960). "A quantitative treatment of electrophilic aromatic substitution". J. Chem. Soc.: 4885–4896. doi:10.1039/jr9600004885.
  17. ^ Ingles, DW; Knowles, JR (1967). "Specificity and stereospecificity of α-chymotrypsin". Biochemical Journal. 104 (2): 369–377. doi:10.1042/bj1040369. PMC 1270596. PMID 6048779.
  18. ^ Knowles, Jeremy R. (1972). "Photogenerated reagents for biological receptor-site labeling". Accounts of Chemical Research. 5 (4): 155–160. doi:10.1021/ar50052a006.
  19. ^ Albery, W. John; Knowles, Jeremy R. (1977). "Efficiency and Evolution of Enzyme Catalysis". Angewandte Chemie International Edition in English. 16 (5): 285–293. doi:10.1002/anie.197702851. PMID 406815.
  20. ^ 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". Biochemistry. 25 (9): 2529–2537. doi:10.1021/bi00357a037. PMID 3755058.
  21. ^ 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". Nature. 275 (5680): 564–565. Bibcode:1978Natur.275..564J. doi:10.1038/275564a0. PMID 357996. S2CID 4203653.
  22. ^ "Chemistry tree". Retrieved 3 April 2021.
  23. ^ "Jeremy Randall Knowles". American Academy of Arts & Sciences. Retrieved 2 May 2022.
  24. ^ "APS Member History". search.amphilsoc.org. Retrieved 2 May 2022.
  25. ^ "Jeremy R. Knowles". www.nasonline.org. Retrieved 2 May 2022.
  26. ^ *HHMI bio Archived 23 November 2005 at the Wayback Machine
  27. ^ "RSC Jeremy Knowles Award". Royal Society of Chemistry. Retrieved 14 November 2014.
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