| Citation | Stephen Halford has made an early major contribution showing that relaxation kinetic analysis can distinguish between mechanisms of protein conformation changes linked to ligand binding. Subsequently he was among the first to correlate solution dynamics with crystal structures. This led to his pioneering application of quantitative biophysical methods to problems previously only examined by qualitative methods of molecular biology. Halford has carried out some of the most detailed mechanistic analyses on various Type II restriction enzymes, providing an understanding of the mechanism of target recognition. The work on EcoRI, SaII, CauI and CauII was important, but the later studies on EcoRV and SfiI were truly ground breaking. His papers are models of how to communicate mechanistic work efficiently. His most recent contributions on the SfiI system has combined imaginative experiments with careful analysis and has revealed novel and unexpected features of this system. The results raise important possibilities for the evolution of Type II systems. The Tn21 resolvase work is also a paradigm for studies of recombination. His investigations on SfiI and Tn21 seem to be converging into a study of recombination. One of Halford's great strengths has been his ability to use x ray structural information in an astoundingly productive fashion. Great thought goes into his experiments and the results are quite clear and make major contributions to our understanding of the mechanisms of restriction enzymes and of protein DNA interaction in general. |