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Updated: Aug 3, 2026

Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry
Published on: March 18, 2012
Structure, dynamics, and catalytic function of dihydrofolate reductase
Jason R Schnell1, H Jane Dyson, Peter E Wright
1Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. schnell@crystal.harvard.edu
Protein dynamics, particularly in E. coli dihydrofolate reductase (DHFR), are crucial for enzyme function. Studies reveal how molecular motions influence DHFR
Area of Science:
- Biochemistry
- Enzymology
- Structural Biology
Background:
- Molecular motions are integral to protein function.
- Escherichia coli dihydrofolate reductase (DHFR) is a model enzyme for studying dynamics-function relationships.
- Extensive structural and mechanistic data exist for E. coli DHFR.
Purpose of the Study:
- To investigate the link between protein dynamics and catalytic function in DHFR.
- To understand how molecular motions influence enzyme activity.
- To map dynamic changes during the DHFR catalytic cycle.
Main Methods:
- Utilized X-ray crystallography, fluorescence, and nuclear magnetic resonance (NMR).
- Employed molecular dynamics (MD) and hybrid quantum/classical dynamics simulations.
- Probed dynamics changes in response to ligand binding, conformational shifts, and mutagenesis.
Main Results:
- Detailed mapping of conformational and dynamic changes in DHFR.
- Identified specific protein motions relevant to the catalytic cycle.
- Demonstrated alterations in dynamics upon ligand binding and mutagenesis.
Conclusions:
- Protein dynamics play a significant role in DHFR's catalytic activity.
- Understanding enzyme motions provides new insights into biochemical mechanisms.
- DHFR serves as a key system for elucidating dynamics-function interplay.
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