You are not currently logged in.
Access your personal account or get JSTOR access through your library or other institution:
If You Use a Screen ReaderThis content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Incorrect Nucleotide Insertion at the Active Site of a G:A Mismatch Catalyzed by DNA Polymerase β
Ping Lin, Vinod K. Batra, Lars C. Pedersen, William A. Beard, Samuel H. Wilson and Lee G. Pedersen
Proceedings of the National Academy of Sciences of the United States of America
Vol. 105, No. 15 (Apr. 15, 2008), pp. 5670-5674
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25461666
Page Count: 5
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Preview not available
Based on a recent ternary complex crystal structure of human DNA polymerase β with a G:A mismatch in the active site, we carried out a theoretical investigation of the catalytic mechanism of incorrect nucleotide incorporation using molecular dynamics simulation, quantum mechanics, combined quantum mechanics, and molecular mechanics methods. A two-stage mechanism is proposed with a nonreactive active-site structural rearrangement prechemistry step occurring before the nucleotidyl transfer reaction. The free energy required for formation of the prechemistry state is found to be the major factor contributing to the decrease in the rate of incorrect nucleotide incorporation compared with correct insertion and therefore to fidelity enhancement. Hence, the transition state and reaction barrier for phosphodiester bond formation after the prechemistry state are similar to that for correct insertion reaction. Key residues that provide electrostatic stabilization of the transition state are identified.
Proceedings of the National Academy of Sciences of the United States of America © 2008 National Academy of Sciences