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Binding isotope effects: boon and bane.

Vern L Schramm1

  • 1Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, United States. vern@aecom.yu.edu

Current Opinion in Chemical Biology
|September 18, 2007
PubMed
Summary
This summary is machine-generated.

Binding isotope effects, often overlooked, reveal crucial atomic changes in enzyme-ligand interactions. These measurable effects offer detailed insights into molecular distortions within catalytic sites.

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Area of Science:

  • Biochemistry
  • Enzyme kinetics
  • Chemical physics

Background:

  • Kinetic isotope effects (KIEs) are vital tools for studying enzyme reaction mechanisms, transition state structures, and quantum tunneling.
  • Binding isotope effects (BIEs) are inherent to KIE measurements but frequently assumed to be negligible.
  • Previous research has indicated significant BIEs in enzymes like lactate dehydrogenase and hexokinase.

Purpose of the Study:

  • To highlight the importance and implications of binding isotope effects in enzyme catalysis.
  • To explain the origins and significance of BIEs in ligand-macromolecular interactions.
  • To demonstrate the utility of BIEs in analyzing atomic distortions within enzyme active sites.

Main Methods:

  • Investigating enzyme-ligand interactions using isotope effect measurements.
  • Analyzing the contribution of binding events to observed isotope effects.
  • Characterizing atomic-level changes upon ligand binding through BIEs.

Main Results:

  • Binding isotope effects are surprisingly large and not negligible in many enzyme systems.
  • Ligand binding induces conformational immobilization, bond polarization, and geometry distortion, generating BIEs.
  • BIEs provide high-resolution data on atomic alterations during molecular interactions.

Conclusions:

  • Binding isotope effects are easily measurable and offer detailed insights into ligand-macromolecular interactions.
  • While complicating KIE analysis, BIEs serve as a powerful method for detecting atomic distortions.
  • Understanding BIEs enhances the interpretation of enzyme mechanisms and the design of inhibitors.