Taking Ockham's razor to enzyme dynamics and catalysis

D.R Glowacki, J.N Harvey, A.J Mulholland

Research output: Contribution to journalArticle (Academic Journal)peer-review

205 Citations (Scopus)


The role of protein dynamics in enzyme catalysis is a matter of intense current debate. Enzyme-catalysed reactions that involve significant quantum tunnelling can give rise to experimental kinetic isotope effects with complex temperature dependences, and it has been suggested that standard statistical rate theories, such as transition-state theory, are inadequate for their explanation. Here we introduce aspects of transition-state theory relevant to the study of enzyme reactivity, taking cues from chemical kinetics and dynamics studies of small molecules in the gas phase and in solution — where breakdowns of statistical theories have received significant attention and their origins are relatively better understood. We discuss recent theoretical approaches to understanding enzyme activity and then show how experimental observations for a number of enzymes may be reproduced using a transition-state-theory framework with physically reasonable parameters. Essential to this simple model is the inclusion of multiple conformations with different reactivity.
Translated title of the contributionA simple multi-conformation transition state theory model accounts for enzyme kinetic isotope effects
Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalNature Chemistry
Publication statusPublished - Jan 2012


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