Strategy and tactics in protein chemistry

Abstract

I would like to congratulate British Drug Houses and the Biochemical Society for the idea of in- stituting this prize, because it may give encouragement to scientists who are thinking of developing new methods.A common theme that has run through every talk in the recent symposium on 'British Biochemistry-Past and Present' (Goodwin, 1970) is the recognition of how advances in almost every field have awaited the development of rele- vant methods.For example, Scheme 1 shows a way of looking at the type of studies that have contributed to our knowledge of how enzymes work.Kinetic investigations of the reaction of the pure enzyme with a range of substrates or inhibitors define the phenomena that the structure must explain.The amino acid sequence is part of the structural investigation and provides a rational framework in which residues important in the catalytic activity or specificity can be described.Chemical modification ofthe protein is the main way in which such active groups are discovered.The only method that can at present tell us the tertiary structure is X-ray diffraction, and for this suitable crystals must be grown.A synthesis of such in- formation has so far provided a plausible mechanism for every enzyme studied, but further work will be needed to prove these mechanisms.New methods are the catalysts in each of these investigations, and to be most useful should be applied at the rate-limiting steps.Kinetic informa-