Jeremy R. Knowles
Jeremy Knowles DPhil) | |
---|---|
Known for | Enzyme catalysis |
Awards | Welch Award in Chemistry (1995) Nakanishi Prize (1999) |
Scientific career | |
Fields | Biochemistry |
Institutions | Harvard University California Institute of Technology |
Thesis | Intramolecular effects in aromatic systems (1961) |
Doctoral students | |
Other notable students | Lia Addadi[5] |
Jeremy Randall Knowles
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, who was ousted by now former president Lawrence Summers.[11][12][13]
Biography
Knowles was born in England in 1935, educated at
Career and research
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
Knowles was elected a
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
Knowles married Jane Sheldon Davis in 1960, and together they had three sons.[14]
References
- PMID 678520.
- .
- ^ PMID 4897198.
- PMID 3427057.
- PMID 6354259.
- ^ "Jeremy Randall Knowles". 14 May 2009.
- ^ PMID 18484705.
- ^ Bio from Harvard (from the office of news and public affairs)
- ^ Public biography
- ^ Harvard Crimson Profile
- ^ 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.
- ^ "Harvard Gazette Obituary". Archived from the original on 11 May 2008. Retrieved 4 April 2008.
- ^ Daily Telegraph Obituary
- ^ a b Levens, R.G.C., ed. (1964). Merton College Register 1900-1964. Oxford: Basil Blackwell. p. 511.
- EThOS uk.bl.ethos.710173.
- .
- PMID 6048779.
- .
- PMID 406815.
- PMID 3755058.
- S2CID 4203653.
- ^ "Chemistry tree". Retrieved 3 April 2021.
- ^ "Jeremy Randall Knowles". American Academy of Arts & Sciences. Retrieved 2 May 2022.
- ^ "APS Member History". search.amphilsoc.org. Retrieved 2 May 2022.
- ^ "Jeremy R. Knowles". www.nasonline.org. Retrieved 2 May 2022.
- ^ *HHMI bio Archived 23 November 2005 at the Wayback Machine
- ^ "RSC Jeremy Knowles Award". Royal Society of Chemistry. Retrieved 14 November 2014.