3ngd | pdb_00003ngd

Structural Basis for Proficient Incorporation of dTTP Opposite O6-methylguanine by Human DNA Polymerase Iota

spinqualitylabelsall models 3ngd, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ngd 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: DCP NonStd Res: 6OG, DOC Related: 2alz, 3epg, 3epi, 2fll, 3nge 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 O(6)-methylguanine (O(6)-methylG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, even physiological ones (e.g. S-adenosylmethionine). The efficiency of a truncated, catalytic DNA polymerase iota core enzyme was determined for nucleoside triphosphate incorporation opposite O(6)-methylG, using steady-state kinetic analyses. The results presented here corroborate previous work from this laboratory using full-length pol iota, which showed that dTTP incorporation occurs with high efficiency opposite O(6)-methylG. Misincorporation of dTTP opposite O(6)-methylG occurred with approximately 6-fold higher efficiency than incorporation of dCTP. Crystal structures of the truncated form of pol iota with O(6)-methylG as the template base and incoming dCTP or dTTP were solved and showed that O(6)-methylG is rotated into the syn conformation in the pol iota active site and that dTTP misincorporation by pol iota is the result of Hoogsteen base pairing with the adduct. Both dCTP and dTTP base paired with the Hoogsteen edge of O(6)-methylG. A single, short hydrogen bond formed between the N3 atom of dTTP and the N7 atom of O(6)-methylG. Protonation of the N3 atom of dCTP and bifurcation of the N3 hydrogen between the N7 and O(6) atoms of O(6)-methylG allow base pairing of the lesion with dCTP. We conclude that differences in the Hoogsteen hydrogen bonding between nucleotides is the main factor in the preferential selectivity of dTTP opposite O(6)-methylG by human pol iota, in contrast to the mispairing modes observed previously for O(6)-methylG in the structures of the model DNA polymerases Sulfolobus solfataricus Dpo4 and Bacillus stearothermophilus DNA polymerase I. Structural basis for proficient incorporation of dTTP opposite O6-methylguanine by human DNA polymerase iota.,Pence MG, Choi JY, Egli M, Guengerich FP J Biol Chem. 2010 Dec 24;285(52):40666-72. Epub 2010 Oct 20. PMID:20961860 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase

Proteopedia Page Contributors and Editors (what is this?)

OCA