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Multiscale Sampling of a Heterogeneous Water/Metal Catalyst Interface using Density Functional Theory and Force-Field Molecular Dynamics
Published on: April 12, 2019
Solvent-mediated proton transfer in catalysis by carbonic anhydrase
David N Silverman1, Robert McKenna
1Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610, USA. silvermn@college.med.ufl.edu
Accounts of Chemical Research
|June 7, 2007
Summary
Carbonic anhydrase catalysis utilizes a mobile His64 residue and surrounding residues to facilitate rapid proton transfer, crucial for enzyme function.
Area of Science:
- Biochemistry
- Enzymology
- Structural Biology
Background:
- Proton transfer is vital in biological macromolecules like bacteriorhodopsin.
- Carbonic anhydrase serves as a model system for studying proton translocation mechanisms.
Purpose of the Study:
- To elucidate the detailed mechanism of proton transfer in carbonic anhydrase catalysis.
- To investigate the role of His64 and surrounding residues in facilitating proton translocation.
Main Methods:
- High-resolution X-ray crystallography.
- Enzyme kinetics measurements.
- Analysis of residue-mediated proton shuttle properties.
Main Results:
- His64 exhibits structural mobility, enhancing proton transfer between the active site and solvent.
- Residues fine-tune the imidazole side chain of His64, affecting its pK(a) and conformation.
- Ordered solvent molecules and His64 interactions are sensitive to the active-site environment.
- Efficient proton transfer rates up to 10(6) s(-1) were observed.
Conclusions:
- The structural mobility of His64 and precise tuning by active-site residues are key to efficient proton transfer in carbonic anhydrase.
- These factors collectively enable the rapid catalytic rates essential for enzyme function.
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