4b9m

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Structure of the high fidelity DNA polymerase I with an oxidative formamidopyrimidine-dA DNA lesion -thymine basepair in the post- insertion site.Structure of the high fidelity DNA polymerase I with an oxidative formamidopyrimidine-dA DNA lesion -thymine basepair in the post- insertion site.

Structural highlights

4b9m is a 3 chain structure with sequence from Geobacillus stearothermophilus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.05Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

E1C9K5_GEOSE

Publication Abstract from PubMed

8-Oxopurines (8-oxodG and 8-oxodA) and formamidopyrimidines (FaPydG and FaPydA) are major oxidative DNA lesions involved in cancer development and aging. Their mutagenicity is believed to result from a conformational shift of the N9-C1' glycosidic bonds from anti to syn, which allows the lesions to form noncanonical Hoogsteen-type base pairs with incoming triphosphates during DNA replication. Here we present biochemical data and what are to our knowledge the first crystal structures of carbocyclic FaPydA and FaPydG containing DNA in complex with a high-fidelity polymerase. Crystallographic snapshots show that the cFaPy lesions keep the anti geometry of the glycosidic bond during error-free and error-prone replication. The observed dG.dC-->dT.dA transversion mutations are the result of base shifting and tautomerization.

Unexpected non-Hoogsteen-based mutagenicity mechanism of FaPy-DNA lesions.,Gehrke TH, Lischke U, Gasteiger KL, Schneider S, Arnold S, Muller HC, Stephenson DS, Zipse H, Carell T Nat Chem Biol. 2013 May 19. doi: 10.1038/nchembio.1254. PMID:23685671[1]

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

See Also

References

  1. Gehrke TH, Lischke U, Gasteiger KL, Schneider S, Arnold S, Muller HC, Stephenson DS, Zipse H, Carell T. Unexpected non-Hoogsteen-based mutagenicity mechanism of FaPy-DNA lesions. Nat Chem Biol. 2013 May 19. doi: 10.1038/nchembio.1254. PMID:23685671 doi:10.1038/nchembio.1254

4b9m, resolution 2.05Å

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OCA