3m9m

Crystal Structure of Dpo4 in complex with DNA containing the major cisplatin lesion

spinqualitylabelsall models 3m9m, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3m9m is a 3 chain structure with sequence from Sulfolobus solfataricus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, CPT, CTP, GOL Related: 3m9n, 3m9o Gene: dbh, dpo4, SSO2448 (Sulfolobus solfataricus) Activity: DNA-directed DNA polymerase, with EC number 2.7.7.7 Resources: FirstGlance, OCA, RCSB, PDBsum 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 Y-family DNA polymerases bypass Pt-GG, the cisplatin-DNA double-base lesion, contributing to the cisplatin resistance in tumour cells. To reveal the mechanism, we determined three structures of the Y-family DNA polymerase, Dpo4, in complex with Pt-GG DNA. The crystallographic snapshots show three stages of lesion bypass: the nucleotide insertions opposite the 3'G (first insertion) and 5'G (second insertion) of Pt-GG, and the primer extension beyond the lesion site. We observed a dynamic process, in which the lesion was converted from an open and angular conformation at the first insertion to a depressed and nearly parallel conformation at the subsequent reaction stages to fit into the active site of Dpo4. The DNA translocation-coupled conformational change may account for additional inhibition on the second insertion reaction. The structures illustrate that Pt-GG disturbs the replicating base pair in the active site, which reduces the catalytic efficiency and fidelity. The in vivo relevance of Dpo4-mediated Pt-GG bypass was addressed by a dpo-4 knockout strain of Sulfolobus solfataricus, which exhibits enhanced sensitivity to cisplatin and proteomic alterations consistent with genomic stress. Structural insight into dynamic bypass of the major cisplatin-DNA adduct by Y-family polymerase Dpo4.,Wong JH, Brown JA, Suo Z, Blum P, Nohmi T, Ling H EMBO J. 2010 Jun 16;29(12):2059-69. Epub 2010 May 28. PMID:20512114 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase

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