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.

Comments

© 2008 the authors. Original published version available at http://doi.org/10.1073/pnas.0809989106.

Evans, R., Davies, D., Bullard, R., et al. Structure of PolC Reveals Unique DNA Binding and Fidelity Determinants. Proceedings of the National Academy of Sciences of the United States of America 2008, vol. 105, 20695-20700.

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

Included in

Chemistry Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.