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Catalysis by entropic guidance from enzymes
1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-1333, USA.
Biochemistry
|December 3, 1996
Summary
Enzyme binding alters cofactor NADH
Area of Science:
- Biochemistry
- Enzymology
- Computational Biology
Background:
- Enzymatic catalysis involves stabilization and proximity effects.
- Average structures from crystallography/NMR miss transient catalytic features.
Purpose of the Study:
- Investigate catalytically relevant properties using molecular dynamics.
- Reveal how enzyme binding affects cofactor conformational fluctuations.
Main Methods:
- Molecular dynamics simulations of enzyme-ligand complexes.
- Analysis of cofactor conformational dynamics and thermal fluctuations.
Main Results:
- Lactate dehydrogenase (LDH) binding alters NADH conformational fluctuations.
- Thermal motions generate transition-state-like structures.
- Alterations are stereospecific, correlating with hydride transfer stereospecificity.
Conclusions:
- Enzymes funnel conformers to the transition state.
- Enzymatic roles include reducing the entropic activation barrier.
- Specific motions enhance transition state formation.