2w8l

Y-family DNA polymerase Dpo4 bypassing N2-naphthyl-guanine adduct in anti orientation

spinqualitylabelsall models 2w8l, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w8l is a 3 chain structure with sequence from Saccharolobus solfataricus P2. This structure supersedes the now removed PDB entry 2v4t. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Ligands: DGT, DOC, MG, N2G Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DPO4_SACS2 Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis. 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 In contrast to replicative DNA polymerases, Sulfolobus solfataricus Dpo4 showed a limited decrease in catalytic efficiency (k(cat)/Km) for insertion of dCTP opposite a series of N2-alkylguanine templates of increasing size from (methyl (Me) to (9-anthracenyl)-Me (Anth)). Fidelity was maintained with increasing size up to (2-naphthyl)-Me (Naph). The catalytic efficiency increased slightly going from the N2-NaphG to the N2-AnthG substrate, at the cost of fidelity. Pre-steady-state kinetic bursts were observed for dCTP incorporation throughout the series (N2-MeG to N2-AnthG), with a decrease in the burst amplitude and k(pol), the rate of single-turnover incorporation. The pre-steady-state kinetic courses with G and all of the six N2-alkyl G adducts could be fit to a general DNA polymerase scheme to which was added an inactive complex in equilibrium with the active ternary Dpo4.DNA.dNTP complex, and only the rates of equilibrium with the inactive complex and phosphodiester bond formation were altered. Two crystal structures of Dpo4 with a template N2-NaphG (in a post-insertion register opposite a 3'-terminal C in the primer) were solved. One showed N2-NaphG in a syn conformation, with the naphthyl group located between the template and the Dpo4 "little finger" domain. The Hoogsteen face was within hydrogen bonding distance of the N4 atoms of the cytosine opposite N2-NaphG and the cytosine at the -2 position. The second structure showed N2-Naph G in an anti conformation with the primer terminus largely disordered. Collectively these results explain the versatility of Dpo4 in bypassing bulky G lesions. Versatility of Y-family Sulfolobus solfataricus DNA polymerase Dpo4 in translesion synthesis past bulky N2-alkylguanine adducts.,Zhang H, Eoff RL, Kozekov ID, Rizzo CJ, Egli M, Guengerich FP J Biol Chem. 2009 Feb 6;284(6):3563-76. Epub 2008 Dec 4. PMID:19059910 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase 3D structures

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