4pha | pdb_00004pha

Structure of human DNA polymerase beta complexed with A in the template base paired with incoming non-hydrolyzable CTP

spinqualitylabelsall models 4pha, resolution 2.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pha is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0KX, MG, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DPOLB_HUMAN Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases. Publication Abstract from PubMed To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase beta (polbeta), we report four crystal structures of polbeta complexed with dG*dTTP and dA*dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg2+-bound ground-state structures show that the dA*dCTP-Mg2+ complex adopts an 'intermediate' protein conformation while the dG*dTTP-Mg2+ complex adopts an open protein conformation. The Mn2+-bound 'pre-chemistry-state' structures show that the dA*dCTP-Mn2+ complex is structurally very similar to the dA*dCTP-Mg2+ complex, whereas the dG*dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson-Crick-like dG*dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polbeta increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polbeta appears to allow only a Watson-Crick-like conformation for purine*pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson-Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polbeta. The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase beta,Koag MC, Nam K, Lee S Nucleic Acids Res. 2014 Sep 8. pii: gku789. PMID:25200079 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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