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[10] Mechanism-based enzyme inactivators

化学 机制(生物学) 生物化学 哲学 认识论
作者
Richard B. Silverman
出处
期刊:Methods in Enzymology [Academic Press]
卷期号:: 240-283 被引量:374
标识
DOI:10.1016/0076-6879(95)49038-8
摘要

Publisher Summary An enzyme inactivator, in general, is a compound that produces irreversible inhibition of the enzyme— that is, it irreversibly prevents the enzyme from catalyzing its reaction. Irreversible in this context, however, does not necessarily mean that the enzyme activity never returns only that the enzyme becomes dysfunctional for an extended (but unspecified) period of time. A mechanism-based enzyme inactivator, by the definition used here, is a compound that is transformed by the catalytic machinery of the enzyme into a species that acts as an affinity labeling agent, a transition state analog, or a tight-binding inhibitor (either covalent or noncovalent) prior to release from the enzyme. Mechanism-based enzyme inactivation is a powerful tool for the studies of enzyme mechanisms and mechanisms of enzyme inactivation, by small molecules. Mechanistic hypotheses can be tested by appropriate molecular design, utilizing the isotopically labeled analogs, to permit the elucidation of the structures of metabolites produced and to determine the portions of the mechanism-based inactivators that become covalently attached to the target enzyme. This approach to the studies of enzyme mechanisms is well suited for those who are geared more to the organic chemistry of enzymecatalyzed reactions and who have insights into the chemical machinery of active sites of enzymes. The use of mechanism-based enzyme inactivators is yet another of the very important methods in enzymology.
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