3in5

Structure of human DNA polymerase kappa inserting dATP opposite an 8-oxoG DNA lesion

spinqualitylabelsall models 3in5, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3in5 is a 6 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 3hed. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: 8OG, ATP, DOC, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function POLK_HUMAN DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. 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 BACKGROUND: Oxygen-free radicals formed during normal aerobic cellular metabolism attack bases in DNA and 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the major lesions formed. It is amongst the most mutagenic lesions in cells because of its dual coding potential, wherein 8-oxoG(syn) can pair with an A in addition to normal base pairing of 8-oxoG(anti) with a C. Human DNA polymerase kappa (Polkappa) is a member of the newly discovered Y-family of DNA polymerases that possess the ability to replicate through DNA lesions. To understand the basis of Polkappa's preference for insertion of an A opposite 8-oxoG lesion, we have solved the structure of Polkappa in ternary complex with a template-primer presenting 8-oxoG in the active site and with dATP as the incoming nucleotide. METHODOLOGY AND PRINCIPAL FINDINGS: We show that the Polkappa active site is well-adapted to accommodate 8-oxoG in the syn conformation. That is, the polymerase and the bound template-primer are almost identical in their conformations to that in the ternary complex with undamaged DNA. There is no steric hindrance to accommodating 8-oxoG in the syn conformation for Hoogsteen base-paring with incoming dATP. CONCLUSIONS AND SIGNIFICANCE: The structure we present here is the first for a eukaryotic translesion synthesis (TLS) DNA polymerase with an 8-oxoG:A base pair in the active site. The structure shows why Polkappa is more efficient at inserting an A opposite the 8-oxoG lesion than a C. The structure also provides a basis for why Polkappa is more efficient at inserting an A opposite the lesion than other Y-family DNA polymerases. Structure of human DNA polymerase kappa inserting dATP opposite an 8-OxoG DNA lesion.,Vasquez-Del Carpio R, Silverstein TD, Lone S, Swan MK, Choudhury JR, Johnson RE, Prakash S, Prakash L, Aggarwal AK PLoS One. 2009 Jun 2;4(6):e5766. PMID:19492058 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase 3D structures

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