Document Type
Article
Publication Date
12-29-2008
Abstract
PolC is the polymerase responsible for genome duplication in many Gram-positive bacteria and represents an attractive target for antibacterial development. We have determined the 2.4-Å resolution crystal structure of Geobacillus kaustophilus PolC in a ternary complex with DNA and dGTP. The structure reveals nascent base pair interactions that lead to highly accurate nucleotide incorporation. A unique β-strand motif in the PolC thumb domain contacts the minor groove, allowing replication errors to be sensed up to 8 nt upstream of the active site. PolC exhibits the potential for large-scale conformational flexibility, which could encompass the catalytic residues. The structure suggests a mechanism by which the active site can communicate with the rest of the replisome to trigger proofreading after nucleotide misincorporation, leading to an integrated model for controlling the dynamic switch between replicative and repair polymerases. This ternary complex of a cellular replicative polymerase affords insights into polymerase fidelity, evolution, and structural diversity.
Recommended Citation
Evans, R. J., Davies, D. R., Bullard, J. M., Christensen, J., Green, L. S., Guiles, J. W., Pata, J. D., Ribble, W. K., Janjic, N., & Jarvis, T. C. (2008). Structure of PolC reveals unique DNA binding and fidelity determinants. Proceedings of the National Academy of Sciences, 105(52), 20695. https://doi.org/10.1073/pnas.0809989106
First Page
20695
Last Page
20700
Publication Title
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.0809989106
Comments
© 2008 the authors. Original published version available at http://doi.org/10.1073/pnas.0809989106