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Updated: Jul 15, 2026
06:18
Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue
Published on: June 21, 2018
Ligand binding and protein dynamics in lactate dehydrogenase
J R Exequiel T Pineda1, Robert Callender, Steven D Schwartz
1Department of Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA.
Biophysical Journal
|May 8, 2007
Summary
Lactate dehydrogenase (LDH) utilizes a select-fit mechanism for substrate binding, involving transiently open protein conformations. Molecular dynamics reveal subtle rearrangements, not unfolding, enable these binding-competent states.
Area of Science:
- Biochemistry
- Molecular Biology
- Computational Chemistry
Background:
- Recent studies propose lactate dehydrogenase (LDH) binds substrates via an encounter complex.
- A select-fit mechanism suggests only a subset of LDH/NADH complexes are binding-competent.
Purpose of the Study:
- To explore structural variations in the LDH/NADH binary complex using molecular dynamics.
- To identify binding-competent conformations consistent with experimental data.
Main Methods:
- Molecular dynamics simulations (2.148 ns).
- Analysis of protein conformations and active site accessibility.
Main Results:
- LDH/NADH samples diverse conformations, including some with solvent-accessible active sites.
- These conformations involve subtle protein and water rearrangements, not large-scale unfolding.
- Mobile loop flexibility and multiple binding pathways are suggested.
Conclusions:
- Binding-competent states arise from minor structural shifts, facilitating ligand access to deep active sites.
- Observed heat capacity changes are explained by altered solvation and hydrogen bond rearrangements.
- This binding strategy may be crucial for efficient ligand delivery in deep pockets.
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