David C. Phillips
Wolf Prize Laureate in Chemistry 1987
David C. Phillips
Affiliation at the time of the award:
University of Oxford, United Kingdom
“for their contributions to protein X-ray crystallography and to the elucidation of structures of enzymes and their mechanisms of action”.
The first enzymes whose 3-dimensional structures were solved by X-ray crystallography were lysozyme by David Phillips in 1965, and chymotrypsin, a larger molecule, by David Blow in 1967. These studies showed how enzymes perform biological catalysis by mobilising their substrates at the active site of the enzyme and gave definite information and ideas about the detailed chemistry of their action. Thus, for the first time it was possible to interpret the catalytic mechanism in stereochemical terms. Both men have also made significant contributions to the tecniques of protein crystallography.
Phillips and Blow have between them pioneered experimental and analytical methods that have contributed to the developments of protein crystallography.
Professor David C. Phillips introduced the use of an automatic diffractometer (together with Arndt) for the precise measurements of the large amount of X-ray data given by a protein, which was the precursor for further automation in the field. Phillips and his team solved not only the structure of lysozyme, but also the complex with its substrate which led to the identification of a specific site and showed a distortion of the substrate towards the transition state. (Many features of the local chemistry of the interaction have since been found in other enzymes). In subsequent work Phillips has determined the structure of their enzymes, most notably triosephosphate isomerase, which was another land-mark in complex enzyme structure.