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Enzymatic tunneling and kinetic isotope effects: chemistry at the crossroads
Author(s) -
Sen Arundhuti,
Kohen Am
Publication year - 2010
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1633
Subject(s) - chemistry , kinetic isotope effect , formate dehydrogenase , quantum tunnelling , dihydrofolate reductase , enzyme catalysis , alcohol dehydrogenase , kinetic energy , enzyme , formate , physical organic chemistry , computational chemistry , chemical physics , biophysical chemistry , catalysis , organic chemistry , deuterium , biochemistry , quantum mechanics , physics
Abstract Kinetic isotope effects (KIEs), originally a tool for the physical organic chemist and mechanistic enzymologist, have been instrumental in furthering our understanding of quantum‐mechanical hydrogen tunneling in enzymatic systems. This review focuses on the use of KIE studies to investigate this phenomenon in enzyme‐catalyzed reactions. A number of enzymes wherein KIEs have been used as a probe for H‐tunneling are discussed, including dihydrofolate reductase (DHFR), alcohol dehydrogenase (ADH), and formate dehydrogenase (FDH). Particular emphasis has been placed on the significance of KIE results in exposing the chemical H‐transfer step in the complex kinetic cascades typical to these systems, as well as on questions regarding the influence of protein dynamics on tunneling and, consequently, on the whole enzymatic reaction. Copyright © 2009 John Wiley & Sons, Ltd.