Orchestration of cooperative events in DNA synthesis and repair mechanism unraveled by transition path sampling of DNA polymerase beta's closing.

ABSTRACT: Our application of transition path sampling to a complex biomolecular system in explicit solvent, the closing transition of DNA polymerase beta, unravels atomic and energetic details of the conformational change that precedes the chemical reaction of nucleotide incorporation. The computed reaction profile offers detailed mechanistic insights into, as well as kinetic information on, the complex process essential for DNA synthesis and repair. The five identified transition states extend available experimental and modeling data by revealing highly cooperative dynamics and critical roles of key residues (Arg-258, Phe-272, Asp-192, and Tyr-271) in the enzyme's function. The collective cascade of these sequential conformational changes brings the DNA/DNA polymerase beta system to a state nearly

SUBMITTER: Radhakrishnan R 

PROVIDER: S-EPMC395907 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature