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993 a.a.
_MN
_ZN
 N deoxynucleoside triphosphate |
= |
 N diphosphate |
+ |
{DNA}(N) |
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Key reference
DOI no: 10.1073/pnas.0809989106 Proc Natl Acad Sci U S A 105:20695-20700 (2008) PubMed id: 19106298
Structure of PolC reveals unique DNA binding and fidelity determinants. R.J.Evans, D.R.Davies, J.M.Bullard, J.Christensen, L.S.Green, J.W.Guiles, J.D.Pata, W.K.Ribble, N.Janjic, T.C.Jarvis. 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-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.
Selected figure(s)
Figure 2.
PHP β-barrel architecture. Schematic representations are shown of canonical PHP (αβ)[7]-barrel (Left) (see Fig. S3), the PolC PHP domain (Center), and the TaqDnaE PHP domain [Right, based on Protein Data Bank (PDB) ID code 2HPI]. Red circles indicate the locations of metal-chelating residues. Filled red circles indicate the locations of metal-chelating residues that are conserved between PolC and TaqDnaE, open circles indicate the locations of metal-chelating residues in PolC and TaqDnaE that are not conserved in EcoDnaE.Figure 4.
Comparison of polymerase active sites from the β-NT and classical superfamilies. The active sites and DNA substrates are shown from PolC (colored as in Fig. 1) and TaqDnaE (white; PDB ID code 3E0D) C family polymerases (A), Polβ (PDB ID code 2FMP), an X family polymerase (B), and RB69 (PDB ID code 1IG9), a B family polymerase (C). (B and C) Palms are colored magenta, and fingers are colored blue.Figures were selected by the author.
Literature references that cite this PDB file's key reference
PubMed id Reference
19718023 M.K.Swan, R.E.Johnson, L.Prakash, S.Prakash, and A.K.Aggarwal (2009).
Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase delta.Nat Struct Mol Biol, 16, 979-986.
PDB code: 3iay
19106294 M.H.Lamers, and M.O'Donnell (2008).
A consensus view of DNA binding by the C family of replicative DNA polymerases.Proc Natl Acad Sci U S A, 105, 20565-20566. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.
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