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Article: Highly Organized but Pliant Active Site of DNA Polymerase [beta]: Compensatory Mechanisms in Mutant Enzymes Revealed by Dynamics Simulations and Energy Analyses
- Article from:
- Biophysical Journal
- Article date:
- June 1, 2004
- Author:
CopyrightCopyright Biophysical Society Jun 2004. Provided by ProQuest LLC. (Hide copyright information)
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ABSTRACT
To link conformational transitions noted for DNA polymerases with kinetic results describing catalytic efficiency and fidelity, we investigate the role of key DNA polymerase [beta] residues on subdomain motion through simulations of five single-residue mutants: Arg-283-Ala, Tyr-271-Ala, Asp-276-Val, Arg-258-Lys, and Arg-258-Ala. Since a movement toward a closed state was only observed for R258A, we suggest that Arg^sup 258^ is crucial in modulating motion preceding chemistry. Analyses of protein/DNA interactions in the mutant active site indicate distinctive hydrogen bonding and van der Waals patterns arising from compensatory structural adjustments. By comparing closed mutant ...