Role of enzyme-substrate flexibility in catalytic activity: an evolutionary perspective.
Site-directed mutagenesis has proved an effective experimental technique to investigate catalytic mechanisms and to determine relations between enzyme structure and function. This article invokes an analytical model based on evolution by mutation and natural selection-Nature's analogue of site-directed mutagenesis-to derive a set of general rules relating enzyme structure and activity. The catalysts are described in terms of the structural parameters, rigidity and flexibility, and the functional variables, reaction rate and substrate specificity. The evolutionary model predicts the following structure-activity relations: (a) rigid enzyme-flexible substrate: large variation in reaction rates, broad substrate specificity; (b) rigid enzyme-rigid substrate: diffusion controlled rates, absolute specificity; (c) flexible enzyme-rigid substrate: intermediate reaction rates, group specificity; (d) flexible enzyme-flexible substrate: slow rates, absolute specificity. Spectroscopic methods and X-ray crystallography now yield important characteristics of enzyme-substrate complexes such as molecular flexibility. The evolutionary analysis we have exploited provides general principles for inferring catalytic activity from structural studies of enzyme-substrate complexes.
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
L
L
Demetrius
D000818:Animals; D002384:Catalysis; D004798:Enzymes / Q000378:metabolism*; D019143:Evolution, Molecular; D008954:Models, Biological; D013329:Structure-Activity Relationship
D004798:Enzymes