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Distinguished for work on mechanisms of enzyme catalysis, especially by stopped and quenched flow methods. He showed that a slow relaxation of chymotrypsin was not a chemical step on the reaction pathway, but a pH-dependent isomerisation between active and inactive forms, and investigated the energetics and equilibria of the transition. He elucidated the leaving-group specificity, leading to a detailed structural interpretation which showed the energetics of "strain" at the binding site. Another experiment dispelled final doubts about the role of a tetrahedral intermediate. More recently Fersht has studied a more complex group of enzymes, the aminoacyl tRNA synthetases. He demonstrated that their precise specificity depends on consecutive independent recognition steps, and under appropriate conditions he trapped a transiently discharged aminoacyl tRNA. Fersht has shown how binding energy can be used to enhance either specificity or rate in an enzymatic reaction, leading to a demonstration of thermodynamic limitations on mechanisms of the "induced fit" type. [18]
Fersht holds honorary doctorates from Uppsala University (1999), [21] Vrije Universiteit Brussel (1999), Weizmann Institute of Science (2004), Hebrew University of Jerusalem (2006), and Aarhus University (2008). He is an Honorary Fellow of Darwin College, Cambridge (2014) and Jesus College, Cambridge (2017). [10]
Fersht has received many prizes and medals including: the FEBS Anniversary Prize; Novo Biotechnology Award; Charmian Medal of the Royal Society of Chemistry; Max Tishler Lecture and Prize Harvard University; The Datta Lectureship and Medal of the Federation of European Biochemical Societies; Jubilee Lecture and the Harden Medal of the Biochemical Society; Feldberg Foundation Prize, Distinguished Service Award, Miami Nature Biotechnology Winter Symposium; Christian B. Anfinsen Award of the Protein Society; Natural Products Award of the Royal Society of Chemistry, Stein and Moore Award of the Protein Society; [22] [23] Bader Award of the American Chemical Society; Kaj Ulrik Linderstrøm-Lang Prize and Medal; Bijvoet Medal of the Bijvoet Center for Biomolecular Research of Utrecht University in 2008 and the Gilbert N. Lewis Medal University of California, Berkeley, and the Wilhelm Exner Medal in 2009. [24]
In 2003 he was knighted for his pioneering work on protein science. [10] His citation on election to the Academy of Medical Sciences reads:
Herchel Smith Professor of Organic Chemistry at the MRC Centre for Protein Engineering, Cambridge, Sir Alan is one of the world's leading protein scientists. He was elected to the Royal Society in his late 30s in 1983 for his work illuminating enzymic catalysis and how enzymes attain high fidelity in the translation of the genetic code. Subsequently he was one of the pioneering founders of protein engineering, developing it as an analytical procedure for understanding interactions in proteins and enzyme catalysis. This radical new approach unravelled the relationships between the structure, activity and function of proteins. The full power of his methods became apparent in his seminal and far reaching contributions to the field of protein folding and stability. These studies opened the way to development of novel therapies in cancer and other diseases. He currently works on mutations that affect the stability and activity of the tumour suppressor p53 and how mutants may be "rescued" by small molecule drugs. His contributions have been widely recognised nationally and internationally by prizes for both chemistry and molecular biology, and by memberships of foreign academies. [20]
In August 2020 he was awarded the Copley Medal of The Royal Society, for his development and application of methods of protein engineering to provide descriptions of protein folding pathways at atomic resolution. [25]
Fersht married Marilyn Persell in 1966 and has one son and one daughter. [10] His recreations include chess, [26] [27] horology and wildlife photography. [10]
Sir Gregory Paul Winter is a Nobel Prize-winning English molecular biologist best known for his work on the therapeutic use of monoclonal antibodies. His research career has been based almost entirely at the MRC Laboratory of Molecular Biology and the MRC Centre for Protein Engineering, in Cambridge, England.
Sir John Ernest Walker is a British chemist who won the Nobel Prize in Chemistry in 1997. As of 2015 Walker is Emeritus Director and Professor at the MRC Mitochondrial Biology Unit in Cambridge, and a Fellow of Sidney Sussex College, Cambridge.
Michael Levitt, is a South African-born biophysicist and a professor of structural biology at Stanford University, a position he has held since 1987. Levitt received the 2013 Nobel Prize in Chemistry, together with Martin Karplus and Arieh Warshel, for "the development of multiscale models for complex chemical systems". In 2018, Levitt was a founding co-editor of the Annual Review of Biomedical Data Science.
Barnase (a portmanteau of "BActerial" "RiboNucleASE") is a bacterial protein that consists of 110 amino acids and has ribonuclease activity. It is synthesized and secreted by the bacterium Bacillus amyloliquefaciens, but is lethal to the cell when expressed without its inhibitor barstar. The inhibitor binds to and occludes the ribonuclease active site, preventing barnase from damaging the cell's RNA after it has been synthesized but before it has been secreted. The barnase/barstar complex is noted for its extraordinarily tight protein-protein binding, with an on-rate of 108s−1M−1.
Richard Henderson is a British molecular biologist and biophysicist and pioneer in the field of electron microscopy of biological molecules. Henderson shared the Nobel Prize in Chemistry in 2017 with Jacques Dubochet and Joachim Frank. "Thanks to his work, we can look at individual atoms of living nature, thanks to cryo-electron microscopes we can see details without destroying samples, and for this he won the Nobel Prize in Chemistry."
Ronald T. Raines is an American chemical biologist. He is the Roger and Georges Firmenich Professor of Natural Products Chemistry at the Massachusetts Institute of Technology. He is known for using ideas and methods of physical organic chemistry to solve important problems in biology.
Reginald John Ellis is a British scientist.
Sir Christopher Martin Dobson was a British chemist, who was the John Humphrey Plummer Professor of Chemical and Structural Biology in the Department of Chemistry at the University of Cambridge, and Master of St John's College, Cambridge.
Stephen James Benkovic is an American chemist known for his contributions to the field of enzymology. He holds the Evan Pugh University Professorship and Eberly Chair in Chemistry at The Pennsylvania State University. He has developed boron compounds that are active pharmacophores against a variety of diseases. Benkovic has concentrated on the assembly and kinetic attributes of the enzymatic machinery that performs DNA replication, DNA repair, and purine biosynthesis.
Sir Shankar Balasubramanian is an Indian-born British chemist and Herchel Smith Professor of Medicinal Chemistry in the Department of Chemistry at the University of Cambridge, Senior Group Leader at the Cancer Research UK Cambridge Institute and Fellow of Trinity College, Cambridge. He is recognised for his contributions in the field of nucleic acids. He is scientific founder of Solexa and biomodal.
Richard Nelson Perham, FRS, FMedSci, FRSA, was Professor of biochemistry at the University of Cambridge, and Master of St John's College, Cambridge 2004–07. He was also editor-in-chief of FEBS Journal from 1998 to 2013.
Sheena Elizabeth Radford is a British biophysicist, and Astbury Professor of Biophysics and a Royal Society Research Professor in the Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology at the University of Leeds. Radford is the Associate Editor of the Journal of Molecular Biology.
James Henderson Naismith is a Scot, Professor of Structural Biology and since autumn of 2023 the Head of the Mathematical, Physical, and Life Science Division (MPLS) Division at the University of Oxford. He was the inaugural Director of the Rosalind Franklin Institute and Director of the Research Complex at Harwell. He previously served as Bishop Wardlaw Professor of Chemical Biology at the University of St Andrews. He was a member of Council of the Royal Society (2021-2022). He is also currently the Vice-Chair of Council of the European X-ray Free Electron Laser and Vice-President (non-clinical) of The Academy of Medical Sciences.
Gideon John Davies is a professor of chemistry in the Structural Biology Laboratory (YSBL) at the University of York, UK. Davies is best known for his ground-breaking studies into carbohydrate-active enzymes, notably analysing the conformational and mechanistic basis for catalysis and applying this for societal benefit. In 2016 Davies was appointed the Royal Society Ken Murray Research Professor at the University of York. Gideon Davies has recently been elected to the Council of the Royal Society.
Jane Clarke is a British biochemist and academic. Since October 2017, she has served as President of Wolfson College, Cambridge. She is also Professor of Molecular Biophysics, a Wellcome Trust Senior Research Fellow in the Department of Chemistry at the University of Cambridge. She was previously a Fellow of Trinity Hall, Cambridge. In 2023, she was elected to the National Academy of Sciences.
Benjamin Guy Davis is a British chemist who is Professor of Chemical biology in the Department of Pharmacology and a member of the Faculty in the Department of Chemistry at the University of Oxford and a Fellow of Pembroke College, Oxford. He holds the role of Science Director for Next Generation Chemistry (2019-2024) and Deputy Director (2020-) at the Rosalind Franklin Institute.
Brian Selby Hartley FRS was a British biochemist. He was Professor of Biochemistry at Imperial College London from 1974 to 1991.
Nigel Shaun Scrutton is a British biochemist and biotechnology innovator known for his work on enzyme catalysis, biophysics and synthetic biology. He is Director of the UK Future Biomanufacturing Research Hub, Director of the Fine and Speciality Chemicals Synthetic Biology Research Centre (SYNBIOCHEM), and Co-founder, Director and Chief Scientific Officer of the 'fuels-from-biology' company C3 Biotechnologies Ltd. He is Professor of Enzymology and Biophysical Chemistry in the Department of Chemistry at the University of Manchester. He is former Director of the Manchester Institute of Biotechnology (MIB).
Sophie Elizabeth Jackson is a British biochemist and Professor of Chemical Biology at the University of Cambridge. Her research considers protein folding and assembly, She is interested in topological knots, molecular complexes and the β barrel protein.
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