Enzyme Specificity and Selectivity

Abstract

Enzymes are exquisitely selective catalysts, capable of choosing a single substrate from a sea of similar compounds. Importantly, specificity is most manifest in the rate that a substrate reacts rather than the affinity of substrate binding. Specificity arises from the three‐dimensional structure of the enzyme‐active site, which is complementary to the transition state of the reaction. In some cases, a good substrate induces an active conformation that is not available to a poor substrate. Enzymes can also contain a second ‘proofreading’ site that further increases selectivity. Specificity is also evident in the way that enzymes control the decomposition of unstable intermediates, restricting their conformation so that the reaction is channelled down one pathway, to yield a single product. Lastly, it is important to recognize that enzyme selectivity is not absolute; the optimization of ‘promiscuous’ activities is an efficient route to the evolution of new enzymes. Key concepts Specificity is most manifest in the rate that a substrate reacts rather than the affinity of substrate binding. The value of k cat /K m is used to assess specificity. The enzyme‐active site is complementary to the transition state, with key residues perfectly aligned to promote the reaction. A good substrate can induce an active enzyme conformation that is not accessed by a poor substrate. Some enzymes contain additional active sites that catalyse proofreading reactions, further enhancing specificity. Enzymes control reaction outcomes by restricting the conformation of substrates and high‐energy intermediates; this is called stereoelectronic control. Enzyme specificity is not absolute; new enzymes evolve via the optimization of ‘promiscuous’ activities.

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