Jeremy Knowles ( born Jeremy Randall Knowles ; April 28, 1935 , Rugby , Yorkshire , UK - April 3, 2008 , Cambridge , Massachusetts , USA ) - English chemist , enzyme .
| Jeremy Knowles | ||
|---|---|---|
| English Jeremy randall knowles | ||
| Date of Birth | ||
| Place of Birth | Rugby , Yorkshire , UK | |
| Date of death | ||
| A place of death | Cambridge , Massachusetts , USA | |
| A country |  United Kingdom | |
| Scientific field | biochemistry , enzymology | |
| Place of work | Harvard University | |
| Alma mater | Oxford University | |
| Famous students | Hagan Bailey | |
| Awards and prizes |
Replicin Award Robert Welch Award Davy Medal | |
Dean of the Department of Science and Arts at Harvard University (1991-2002), member of the Royal Society of London (1977) [2] , foreign member of the US National Academy of Sciences (1988) [3] .
He contributed to the study of the mechanism of work of enzymes such as triose phosphate isomerase, proline racemase, chymotrypsin, beta-lactamase. The Royal Chemical Society established a medal to them. J. Knowles with the goal of "recognizing the importance of inter- and multidisciplinary research in the field of chemistry and life sciences."
Content
- 1 Biography
- 1.1 Childhood
- 1.2 Education
- 1.3 Family and children
- 2 Scientific activities
- 2.1 Career start
- 2.2 Return to Oxford
- 2.3 Years at Harvard
- 3 Awards and Membership
- 4 notes
- 5 Literature
- 6 References
Biography
Childhood
Jeremy Knowles was born on April 28, 1935 in the city of Rugby, Yorkshire , UK, in the family of Kenneth school teacher Charles Knowles (1908-1988) and Dorothy Helen (nee Swinger). Subsequently, Charles Knowles taught economics at the University of Nottingham , and then took a position at the Oxford Institute of Economics and Statistics .
Education
He received his secondary education at Magdalen College in Oxford from 1948 to 1953. After college, he spent two years in the national service in the Royal Air Force (1953-1955) as a pilot officer. After military service, he entered Balli College in Oxford, where he studied chemistry from 1955 to 1959. In 1959, according to the British Classification of Academic Degrees, he received a first-class degree in chemistry.
Family and Children
In 1960, he married the daughter of Herbert John Davis, a professor of English literature at Oxford University - Jane Sheldon Davis. Three sons were born in the marriage - Sebastian, Julius and Timothy. Knowles happily married until his death.
Scientific activity
Career start
After graduating from Balliol College, Knowles continued his research at Richard Norman's Laboratory of Physical Organic Chemistry at Oxford . In 1961, he defended his thesis on the role of superconjugation in aromatic substitution, as well as other intramolecular effects in aromatic systems, and received a doctorate in chemistry . A year earlier, he published his first scientific article in collaboration with the supervisor of studies [4] . In addition, in those same years, he served as a senior fellow at Merton College and lectured at Christ Church in Oxford . In 1962, he temporarily left these positions for doctoral studies at the California Institute of Technology. Initially, his collaboration with Professor George Hammond was supposed, however, Knowles joined the research team of Dr. Brian Jones to study the enzymatic activity of the alpha-chymotrypsin serine protease. It was this work that formed the basis of the first publications of Knowles as an independent researcher [5] . Then Knowles approached the study of pepsin-aspartyl protease, the mechanism of which at that time was unclear [6] . However, his efforts to study this enzyme were not very successful - the mechanism could not even be suggested using the crystallographic structure, and comprehensive data on this protease were obtained only years later. Nevertheless, these first works allowed J. Knowles to gain respect among fellow enzyme scientists.
Return to Oxford
Returning from California, he began the study of the glycolytic enzyme triosophosphatisomerase as an employee of Wadham College. A series of experiments with isotopic substitution of hydrogen made it possible for the first time to publish the energy profile of the free energy of the catalytic reaction [7] [8] .
Years at Harvard
Although Knowles decided to move to the United States in the early 1970s, he continued to analyze the triosophosphatisomerase data obtained at Oxford for a long time. From 1969 to 1971, he worked at Yale University as a visiting professor, and in 1974 he became an employee of Harvard University. At Harvard, he studied the inhibition of lactamase (including clavulanic acid) [9] . He also delved into the study of the kinetics of transfer of the phosphate group using various structural approaches to the study of enzymes. In 1975, Knowles tried to study the mechanism of action of the phosphoglycerate kinase enzyme to find out whether the intermediate phosphorylated enzyme is actually involved in the mechanism or whether there is a direct transfer between adenosine triphosphate (ATP) and phosphoglycerate. After a thorough analysis, Knowles rejected the assumption of an intermediate phosphorylated enzyme. To study the mechanism of phosphate group transfer directly by Knowles, the use of isotope-labeled chiral phosphate monoesters was proposed. This method allowed us to unambiguously track the stereochemistry of the reaction. The configuration was maintained in accordance with the formation of an intermediate phosphorylated enzyme [10] .
The next enzyme after triosephosphatisomerase, for which J. Knowles studied the form of the energetic profile of the reaction, was proline racemase. In 1986, together with Professor Albury, they proved that the rate of catalysis is limited by the interconversions of unbound forms of the enzyme [11] . It was shown that cysteine residues, which perform the function of proton transfer, are involved in the racemization mechanism.
In 1983, J. Knowles received a proposal from the then president of Harvard University - Bock, to take the post of dean of the Faculty of Arts and Sciences. However, he rejected the offer, being not ready to refuse his biochemical studies. However, after a second proposal in 1991, Knowles closed his research laboratory due to a new appointment. His administrative abilities were appreciated by colleagues. Knowles helped create a series of concerts during the lunch break, he supported art as a whole at Harvard.
Awards and Memberships
Jeremy Knowles was a member of the Royal Society of London (1977), the American Academy of Arts and Sciences (1982), the American Philosophical Society (1988), a foreign member of the United States National Academy of Sciences (1988), and trustee of the Howard Hughes Medical Institute (1988). He was an honorary member of Balliol and Wadham College in Oxford. Knowles was awarded the Davy Medal by the Royal Society (1991), the Prelog Medal in Zurich (1989), and was awarded the Bader Prize, the Replicen Prize, and the Nakanishi Prize of the American Chemical Society (1989, 1993, and 1999, respectively). Knowles was also a visiting professor at Oxford in 1983-1984.
In 2008, the Royal Chemical Society established a medal to them. J. Knowles, called to note "the importance of inter- and multidisciplinary research in the field of chemistry and life sciences."
Notes
- ↑ http://web.archive.org/web/20080509044131/http://www.news.harvard.edu:80/gazette/2008/04.03/99-knowles.html
- ↑ Knowles; Jeremy Randall (1935 - 2008 )
- ↑ Jeremy R. Knowles
- ↑ Knowles J., Norman C., Radda G. A quantitative treatment of electrophilic aromatic substitution // J. Chem. Soc. 1960. 4885-4896.
- ↑ Knowles J. The role of methionine in α-chymotrypsin-catalysed reactions // Biochem. J. 1965.180-190.
- ↑ Knowles J. On the mechanism of action of pepsin // Phil. Trans. R. Soc. Lond. 1970.135-146.
- ↑ Albery J., Knowles. J. Deuterium and tritium exchange in enzyme kinetics // Biochemistry. 15. 1976. 5588-5600.
- ↑ Albery J., Knowles. J. Free-energy profile for the reaction catalyzed by triosephosphate isomerase // Biochemistry. 15. 1976. 5627-5631.
- ↑ Easton J., Knowles J. Correlation of the effect of β-lactamase inhibitors on the β-lactamase in growing cultures of gram-negative bacteria with their effect on the isolated β-lactamase // Antimicrob. Agents Chemother. 26.1984. 358-363.
- ↑ Orr A., Knowles J., Simon J., Jones R. Adenosine 5′-O - ([γ-18O] γ-thio) triphosphate chiral at the γ-phosphorus: stereochemical consequences of reactions catalyzed by pyruvate kinase, glycerol kinase, and hexokinase // Proc. Natl Acad. Sci. USA 75. 1978. 2230-2233.
- ↑ Knowles J., Fisher M. Energetics of proline racemase: racemization of unlabeled proline in the unsaturated, saturated and oversaturated regimes // Biochemistry 25.1986. 2529-2537.
Literature
- Biographical Memoirs of Fellows of the Royal Society. 2010.171-187
- Cornish-Bowden A. Jeremy Randall Knowles // Biochemist 30 (3). 2008.46-47.
- Hansen E. Jeremy R. Knowles: the evolution of an enzymologist // Bioorg. Chem. 23. 1977.303-339.