Reexamination of induced fit as a determinant of substrate specificity in enzymatic reactions.
It has been argued that a substrate-induced conformational change involving the orientation of catalytic groups cannot affect the specificity for two substrates in an enzymatic system where the chemical step is rate limiting, because such an induced fit would alter the catalytic efficiency for both to an equal extent. To the contrary, the generalized induced-fit treatment described here shows that when critical substrate-specific conformational changes in the enzyme persist in the transition state, specificity is linked to conformational differences between the reactive complex for a good substrate and the related complex for a poor one. Conformational differences are a determinant of specificity when the reaction proceeds via an "induced-fit" transition state. Our treatment also shows that such conformational changes can enhance the specificity of an enzyme with suboptimal catalytic efficiency. If substrate-dependent conformational differences in a primative enzyme can enhance specificity, evolutionary pressure to increase specificity could inseparably link enzymatic specificity to induced conformational changes.
Department of Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907-1333, USA.
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D002384:Catalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D011487:Protein Conformation; D013379:Substrate Specificity
D004798:Enzymes