Structural enzymology: a quantitative approach
Enzymes are proteins with catalytic properties; they are the products of natural evolution. Enzymes have evolved to catalyse a wide range of reactions with high substrate and reaction selectivity. Both the affinity as well as the catalytic efficiency of enzymes have evolved such as to be optimal for the metabolic requirements of the organism. Consequently most enzymes operate at room temperature, at ambient pressure and under conditions of neutral pH. The rate enhancements achieved by enzymes are enormous, typically in the range of 105 to 108 (Koeller and Wong, 2001), but in extreme cases of the order of 1017 (Radzicka and Wolfenden, 1995; Wolfenden, 1999). From the studies of Wolfenden and others it emerges that enzymes have evolved to bind the high energy transition state much more strongly than the substrate or the product, thus allowing for catalysis to happen. Achieving the detailed understanding of the reaction mechanisms of enzymes is an intellectual challenge. It is also of crucial importance for being able to harness the enormous catalytic power of enzymes for the synthesis of taylor-made compounds in lab scale organic chemistry and large scale industrial processes (Koeller and Wong, 2001). This is particularly important because many naturally evolved enzymes have a substrate and reaction specificity which is different from the reactions of practical importance and consequently wild type enzymes have to be engineered such as to optimize the required substrate and reaction selectivity. Furthermore, precise understanding of the reaction mechanism facilitates the discovery of very tight binding transition state analogues for use as enzyme inhibitors, which are for example potential drugs in medical applications (Schramm, 2005). Principally, three classes of enzymes are being studied, which are triosephosphate isomerases (TIM), CoA-dependent enzymes and prolyl-4-hydroxylases (Figure 1).
Viimeksi päivitetty: 28.10.2016