Structure of PolC reveals unique DNA binding and fidelity determinants

Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20695-700. doi: 10.1073/pnas.0809989106. Epub 2008 Dec 23.


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-A 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 beta-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.

MeSH terms

  • Amino Acid Motifs / physiology
  • Bacillaceae / enzymology*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Catalytic Domain / physiology
  • Crystallography, X-Ray
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / metabolism
  • Genome, Bacterial / physiology
  • Protein Structure, Quaternary / physiology
  • Protein Structure, Tertiary / physiology
  • Structure-Activity Relationship


  • Bacterial Proteins
  • PolC protein, bacteria
  • DNA-Directed DNA Polymerase

Associated data

  • PDB/3F2B
  • PDB/3F2C
  • PDB/3F2D