What Everyone Wanted to Know About Tight Binding and Enzyme Catalysis, but Never Thought of Asking

Abstract

The notions that an enzyme increases the reaction rate of substrates by bringing them together at the active site and by destabilizing them are among the earliest hypotheses for explaining the extraordinary catalytic power of enzymes toward their specific substrates (Haldane 1930; Pauling 1946). These ideas were eclipsed in recent years by advances in our understanding of chemical mechanisms of catalysis and by the elucidation of the three-dimensional structures of enzymes and enzyme-substrate complexes by X-ray diffraction. However, they have received renewed attention in the last few years as it has become apparent that ordinary chemical mechanisms do not provide an adequate explanation for the observed magnitude of enzymic catalysis An important role for physical interactions that are mediated through utilization of the binding energy of specific substrates is suggested, in particular, by the large increases in reaction rate of up to 10¹⁰–10¹³ that are brought about by nonreacting portions of substrates, such as the sugar ring and phosphate of glucose-1-phosphate with phosphoglucomutase and the coenzyme A moiety of succinyl-CoA with coenzyme A transferase (Ray and Long 1976; Ray et al. 1976; Moore 1978; Jencks 1980a).