Our major research programme concerns the folding, stability and activity of proteins. We apply a broad multi-disciplinary approach that combines methods and ideas of molecular biology and physical-organic chemistry. We use techniques including protein engineering, DNA cloning, sequencing and mutagenesis, cell culture, gene and peptide synthesis, spectroscopy, rapid reaction techniques, multi-dimensional NMR (we have a 500, 600, 700 and an 800 MHz spectrometers) and x-ray protein crystallography.

Current major projects include: protein folding, misfolding and disease; drug discovery; and structure-activity relationships of proteins involved in cancer and disease.

Although now emeritus, I am still fully active in research with long term funding, including an MRC Programme Grant.

Publications

Demonstration of two active sites on a monomeric aminoacyl-tRNA synthetase. Possible roles of negative cooperativity and half-of-the-sites reactivity in oligomeric enzymes
AR Fersht
Biochemistry
(2002)
14
Mechanism of the -chymotrypsin-catalyzed hydrolysis of amides. pH dependence of k c and K m . Kinetic detection of an intermediate.
AR Fersht, Y Requena
J Am Chem Soc
(2002)
93
Relationships between apparent binding energies measured in site-directed mutagenesis experiments and energetics of binding and catalysis.
AR Fersht
Biochemistry
(2002)
27
Dissection of the effector-binding site and complementation studies of Escherichia coli phosphofructokinase using site-directed mutagenesis
FT Lau, AR Fersht
Biochemistry
(2002)
28
Assignment of histidine resonances in the 1H NMR (500 MHz) spectrum of subtilisin BPN' using site-directed mutagenesis.
M Bycroft, AR Fersht
Biochemistry
(2002)
27
Metal ion dependence of phosphorothioate ATP analogues in the Bacillus stearothermophilus tyrosyl-tRNA synthetase reaction.
GA Garcia, RJ Leatherbarrow, F Eckstein, AR Fersht
Biochemistry
(2002)
29
Mechanism of aminoacylation of transfer RNA. A pre-steady-state analysis of the reaction pathway catalyzed by the methionyl-tRNA synthetase of Bacillus stearothermophilus
RS Mulvey, AR Fersht
Biochemistry
(2002)
17
Site-directed mutagenesis reveals transition-state stabilization as a general catalytic mechanism for aminoacyl-tRNA synthetases
TJ Borgford, TE Gray, NJ Brand, AR Fersht
Biochemistry
(2002)
26
Establishing the misacylation/deacylation of the tRNA pathway for the editing mechanism of prokaryotic and eukaryotic valyl-tRNA synthetases
AR Fersht, C Dingwall
Biochemistry
(2002)
18
pH Dependence of chymotrypsin catalysis. Appendix. Substrate binding to dimeric α-chymotrypsin studied by x-ray diffraction and the equilibrium method
AR Fersht, M Renard
Biochemistry
(2002)
13