3q8q | pdb_00003q8q

Human DNA polymerase iota incorporating dATP opposite 8-oxo-guanine

spinqualitylabelsall models 3q8q, resolution 2.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3q8q is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DTP, MG NonStd Res: 8OG Related: 3q8p, 3q8s, 3q8r Gene: POLI, RAD30B (Homo sapiens) Activity: DNA-directed DNA polymerase, with EC number 2.7.7.7 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The 8-oxo-guanine (8-oxo-G) lesion is the most abundant and mutagenic oxidative DNA damage existing in the genome. Due to its dual coding nature, 8-oxo-G causes most DNA polymerases to misincorporate adenine. Human Y-family DNA polymerase iota (poliota) preferentially incorporates the correct cytosine nucleotide opposite 8-oxo-G. This unique specificity may contribute to poliota's biological role in cellular protection against oxidative stress. However, the structural basis of this preferential cytosine incorporation is currently unknown. Here we present four crystal structures of poliota in complex with DNA containing an 8-oxo-G lesion, paired with correct dCTP or incorrect dATP, dGTP, and dTTP nucleotides. An exceptionally narrow poliota active site restricts the purine bases in a syn conformation, which prevents the dual coding properties of 8-oxo-G by inhibiting syn/anti conformational equilibrium. More importantly, the 8-oxo-G base in a syn conformation is not mutagenic in poliota because its Hoogsteen edge does not form a stable base pair with dATP in the narrow active site. Instead, the syn 8-oxo-G template base forms the most stable replicating base pair with correct dCTP due to its small pyrimidine base size and enhanced hydrogen bonding with the Hoogsteen edge of 8-oxo-G. In combination with site directed mutagenesis, we show that Gln59 in the finger domain specifically interacts with the additional O(8) atom of the lesion base, which influences nucleotide selection, enzymatic efficiency, and replication stalling at the lesion site. Our work provides the structural mechanism of high-fidelity 8-oxo-G replication by a human DNA polymerase. Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota.,Kirouac KN, Ling H Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3210-5. Epub 2011 Feb 7. PMID:21300901 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase

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