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

Reconstruction by site-directed mutagenesis of the transition state for the activation of tyrosine by the tyrosyl-tRNA synthetase: a mobile loop envelopes the transition state in an induced-fit mechanism
AR Fersht, JW Knill-Jones, H Bedouelle, G Winter
Biochemistry
(2002)
27
Recombinant chymotrypsin inhibitor 2: expression, kinetic analysis of inhibition with alpha-chymotrypsin and wild-type and mutant subtilisin BPN', and protein engineering to investigate inhibitory specificity and mechanism.
C Longstaff, AF Campbell, AR Fersht
Biochemistry
(2002)
29
Kinetic characterization of the recombinant ribonuclease from Bacillus amyloliquefaciens (barnase) and investigation of key residues in catalysis by site-directed mutagenesis.
DE Mossakowska, K Nyberg, AR Fersht
Biochemistry
(2002)
28
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
Protection of an unstable reaction intermediate examined with linear free energy relationships in tyrosyl-tRNA synthetase
TN Wells, AR Fersht
Biochemistry
(2002)
28
Mechanism of chymotrypsin. Structure, reactivity, and nonproductive binding relationships.
J Fastrez, AR Fersht
Biochemistry
(2002)
12
Probing the limits of protein-amino acid side chain recognition with the aminoacyl-tRNA synthetases. Discrimination against phenylalanine by tyrosyl-tRNA synthetases
AR Fersht, JS Shindler, WC Tsui
Biochemistry
(2002)
19
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
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
Dissection of the structure and activity of the tyrosyl-tRNA synthetase by site-directed mutagenesis
AR Fersht
Biochemistry
(2002)
26