Jeremy R. Knowles
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|Jeremy R. Knowles|
|Born||April 28, 1935|
|Died||April 3, 2008(aged 72)|
|Alma mater||Oxford University|
|Doctoral students||Hagan Bayley|
|Known for||Enzyme catalysis|
Jeremy Randall Knowles, CBE, FRS (April 28, 1935 – April 3, 2008) was a professor of chemistry at Harvard University, was Dean of the Harvard University Faculty of Arts and Sciences 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 April 3, 2008 at his home.
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.
Knowles was born in England in 1935, educated at Magdalen College School, Oxford and Balliol College, Oxford (BA 1959, DPhil 1961). He was a Pilot Officer in the Royal Air Force. During his undergraduate he did research in Richard Norman's physical organic chemistry lab. In lab, he studied the electronic effects on the rates of aromatic substitution reactions. In 1960, he became a research lecturer at Oxford. In 1961. He later became Fellow and Tutor at Wadham College, Oxford. In 1961, when he took a post-doctoral fellowship at California Institute of Technology, he began working with George S. Hammond, 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 (see below for description of work). Knowles also was a visiting professor at Yale. in 1974, Knowles moved his research to Harvard and became a permanent professor there.
Knowles married Jane Sheldon Davis in 1960, and they had three sons.
Knowles's research was on the boundary of chemistry and biochemistry, and concerned the rate and specificity of enzyme catalysis and the evolution of protein function. As an enzymologist Knowles studied alpha chymotrypsin and pepsin, 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 reactions.He then began studying glycolytic enzyme trioposephosphate isomerase (TIM). He looked at its ability to interconvert a single substrate and a single product. He found that there was an enediol intermediate produced in the reactions that allowed solvent protons to enter the reaction from the middle instead of only from the substrates or products. He also then researches and found the energy of these intermediates and transition states, which allowed him to study the reaction energetics. He worked with John Albery to study hydrogen isotopes as well while studying TIM. From his research, Knowles was able to make a free energy profile of reaction with TIM in 1976. His profile showed that the transition states of the reaction were all of comparable energy, which then indicated that the enzyme-bound intermediates were all of comparable free energy.
Knowles' next research, based at Harvard University, focussed on Beta Lactamases and their mechanism based inhibitors. He focussed on the stereochemistry of the phosphoryl group transfer reactions. Knowles used a chiral phosphate strategy for pseudo-rotation in the reaction of phosphate mono-ester and of monomeric meta-phosphate.
Later in his research, Knowles found that proline racemase showed similar results to TIM in the profile of the reaction. He was also able to find the consequences of over saturation: interconversion of distinct un-liganded forms of enzyme limit catalysis.
Knowles also found a kinetic isotope experiment that showed whether a reaction proceeds in a stepwise or concerted manner.
In 1972, Knowles found a method for photo-affinity labelling. First, he used antibodies raised in rabbits against a 2-nirto-4-azidophenyl haptenic group. He then did a similar experiment with alpha chymotrypsin. Photo-affinity labelling can be used for mapping sites in homogeneous systems and also for probing on the basis of heterogeneity in systems that are not.
In 1980, Knowles used diazirines instead of arylazides to yield carbenes, which are more reactive.
Awards and honors
Knowles was a Fellow of the Royal Society, the American Academy of Arts and Sciences, the American Philosophical Society, the American Association for the Advancement of Science, and a Foreign Associate of the National Academy of Sciences. 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 American Chemical Society's Arthur 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 CBE in the Queen's Birthday Honours of 1993. He was elected one of nine Trustees of the Howard Hughes Medical Institute in 1998.
- 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. PMID 678520.
- Raines, R. T. (2008). "Jeremy R. Knowles (1935−2008)". ACS Chemical Biology 3 (5): 262–264. doi:10.1021/cb800099n. PMID 18484705.
- Jeremy R. Knowles named Interim Dean of the Faculty of Arts and Sciences, Harvard University Gazette, published 2006-05-22; retrieved 2009-06-10.
- HHMI bio
- Bio from Harvard (from the office of news and public affairs)
- Public biography
- Harvard Crimson Profile
- Harvard Gazette Obituary
- Daily Telegraph Obituary