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Substrate-to-Product Conversion Facilitates Active Site Loop Opening in Yeast Enolase: A Molecular Dynamics Study
Pengfei Li1, Sharon Hammes-Schiffer1
1Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520.
ACS Catalysis
|December 20, 2019
Summary
Yeast enolase loop opening is facilitated by product formation, weakening enzyme-ligand interactions. This mechanism aids product release, offering insights for enzyme design.
Area of Science:
- Biochemistry
- Enzymology
- Structural Biology
Background:
- Yeast enolase is a key metalloenzyme in glycolysis and fermentation.
- Its active site features labile metal ions crucial for catalysis.
Purpose of the Study:
- To elucidate the mechanism of active site loop opening in yeast enolase.
- To understand how substrate-to-product conversion influences loop dynamics.
Main Methods:
- Microsecond molecular dynamics simulations of protein-substrate and protein-product complexes.
- Free energy simulations to quantify loop opening energetics.
Main Results:
- Product formation reduces metal coordination and hydrogen bonds, increasing loop flexibility.
- Loop opening is endergonic with substrate but exergonic with product bound.
- Catalysis weakens loop-ligand interactions, promoting loop opening and product release.
Conclusions:
- Enzyme catalysis in yeast enolase facilitates product release through altered active site loop dynamics.
- Understanding these loop motions can guide future enzyme engineering and design efforts.
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