Physical Organic Model Systems and the Problem of Enzymatic Catalysis
[Book]
Thomas H Fife Affiliation: Department of Biochemistry, University of Southern California, Los Angeles, California 90033, U.S.A.
This chapter discusses physical organic model system and the problem of enzymatic catalysis. It describes chemical model investigations, which relate to three hydrolytic enzymes, α-chymotrypsin, carboxypeptidase, and lysozyme. These enzymes serve as the best examples of the model approach because detailed structural information is available. In each case, the complete amino-acid sequence of the enzyme is known, and the three-dimensional structure has been determined by x-ray crystallographic analysis at 2 Å resolutions. The enzymes have the aliphatic hydroxyl group of serine, the imidazole ring of histidine, and carboxyl groups as catalytically important functional groups at the active sites. The problem resolves itself into determining how such functional groups can participate in the hydrolytic reactions and how the rates of the enzymatic reactions can be accounted for in mechanistic terms. Model studies have made a major contribution towards an understanding of the mechanistic possibilities, which lysozyme might employ. Rate enhancements have been obtained in several simple chemical reactions that are of similar magnitude to those observed in analogous enzyme-catalyzed reactions, and the goal of analyzing the individual factors that can give such large rate accelerations is now within reach.
Thomas H Fife Affiliation: Department of Biochemistry, University of Southern California, Los Angeles, California 90033, U.S.A.
Thomas H Fife Affiliation: Department of Biochemistry, University of Southern California, Los Angeles, California 90033, U.S.A.