| Citation | Distinguished for his contributions concerning the mechanism of action of enzymes. His early work, in the laboratory of H.Gutfreund, related chiefly to glyceraldehydes 3-phosphate dehydrogenase. It included the synthesis of novel organomercurial chromophoric probes for -SH groups and identification of the aldehyde form of glyceraldehydes 3-phosphate, rather than the normally predominant diol form, as the substrate of this enzyme and of aldolase and triosephosphate isomerase. His penetrating studies of the mechanism of the glyceraldehydes 3-phosphate dehydrogenase reaction by transient kinetic methods allowed the identification and measurements of the rates of elementary steps, and gave evidence that all four sites of the tetrameric lobster enzyme are silmultaneously active in catalysis. He is perhaps best known however for his work on the ATPase activity of myosin. After a demonstration by rapid linked-enzyme assay that the rate-limiting step is earlier than product release, he has used a range of optical methods (protein fluorescence; absorption and fluorescence of substrate analogues) and, more recently, oxygen isotope exchange alone or combined with 31P NMR spectroscopy, by which he has demonstrated numerous important features of the ATPase action, including two isomerisation processes in the protein, reversible cleavage of the substrate while bound, and inversion of the chirality of the terminal phosphate in hydrolysis. Largely as a result of these experiments, the chemical events associated with utilisation of ATP are known in greater detail for myosin than for any other biological system. |