Binding isotope effects: boon and bane.

作者: Vern L Schramm

DOI: 10.1016/J.CBPA.2007.07.013

关键词: Computational chemistryHydrideIsotopeIonPurine nucleoside phosphorylaseTransition state analogStereochemistryReaction mechanismMolecular geometryKinetic isotope effectChemistry

摘要: Kinetic isotope effects are increasingly applied to investigate enzyme reactions and have been used understand transition state structure, reaction mechanisms, quantum mechanical hydride ion tunneling design analogue inhibitors. Binding an inherent part of most effect measurements but usually assumed be negligible. More detailed studies established surprisingly large binding with lactate dehydrogenase, hexokinase, thymidine phosphorylase, purine nucleoside phosphorylase. reactants into catalytic sites immobilizes conformationally flexible groups, polarizes bonds, distorts bond angle geometry, all which generate effects. easily measured provide high-resolution information on the atomic changes resulting from ligand–macromolecular interactions. Although complicate kinetic analysis, they also a powerful tool for finding distortion in molecular

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