Binding isotope effects

boon and bane

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)529-536
Number of pages8
JournalCurrent Opinion in Chemical Biology
Volume11
Issue number5
DOIs
StatePublished - Oct 2007

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Isotopes
Purine-Nucleoside Phosphorylase
Thymidine Phosphorylase
Kinetics
Hexokinase
Molecular interactions
L-Lactate Dehydrogenase
Hydrides
Catalytic Domain
Ions
Ligands
Geometry
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Binding isotope effects : boon and bane. / Schramm, Vern L.

In: Current Opinion in Chemical Biology, Vol. 11, No. 5, 10.2007, p. 529-536.

Research output: Contribution to journalArticle

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