1tk8

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T7 DNA polymerase ternary complex with 8 oxo guanosine and dAMP at the elongation site

Structural highlights

1tk8 is a 4 chain structure with sequence from Escherichia coli and Escherichia phage T7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:1PE, 2DA, 8OG, D3T, MES, MG, SO4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPOL_BPT7 Replicates viral genomic DNA. Non-processive DNA polymerase that achieves processivity by binding to host thioredoxin (TrxA). This interaction increases the rate of dNTP incorporation to yield a processivity of approximately 800 nucleotides (nt) per binding event. Interacts with DNA helicase gp4 to coordinate nucleotide polymerization with unwinding of the DNA. The leading strand is synthesized continuously while synthesis of the lagging strand requires the synthesis of oligoribonucleotides by the primase domain of gp4.[1] [2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Accurate DNA replication involves polymerases with high nucleotide selectivity and proofreading activity. We show here why both fidelity mechanisms fail when normally accurate T7 DNA polymerase bypasses the common oxidative lesion 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8oG). The crystal structure of the polymerase with 8oG templating dC insertion shows that the O8 oxygen is tolerated by strong kinking of the DNA template. A model of a corresponding structure with dATP predicts steric and electrostatic clashes that would reduce but not eliminate insertion of dA. The structure of a postinsertional complex shows 8oG(syn).dA (anti) in a Hoogsteen-like base pair at the 3' terminus, and polymerase interactions with the minor groove surface of the mismatch that mimic those with undamaged, matched base pairs. This explains why translesion synthesis is permitted without proofreading of an 8oG.dA mismatch, thus providing insight into the high mutagenic potential of 8oG.

Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase.,Brieba LG, Eichman BF, Kokoska RJ, Doublie S, Kunkel TA, Ellenberger T EMBO J. 2004 Sep 1;23(17):3452-61. Epub 2004 Aug 5. PMID:15297882[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Notarnicola SM, Mulcahy HL, Lee J, Richardson CC. The acidic carboxyl terminus of the bacteriophage T7 gene 4 helicase/primase interacts with T7 DNA polymerase. J Biol Chem. 1997 Jul 18;272(29):18425-33. PMID:9218486
  2. ↑ Zhang H, Lee SJ, Zhu B, Tran NQ, Tabor S, Richardson CC. Helicase-DNA polymerase interaction is critical to initiate leading-strand DNA synthesis. Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9372-7. doi:, 10.1073/pnas.1106678108. Epub 2011 May 23. PMID:21606333 doi:http://dx.doi.org/10.1073/pnas.1106678108
  3. ↑ Brieba LG, Eichman BF, Kokoska RJ, Doublie S, Kunkel TA, Ellenberger T. Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase. EMBO J. 2004 Sep 1;23(17):3452-61. Epub 2004 Aug 5. PMID:15297882 doi:10.1038/sj.emboj.7600354

Contents


PDB ID 1tk8

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OCA

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