2van
Nucleotidyl Transfer Mechanism of Mismatched dNTP Incorporation by DNA Polymerase b by Structural and Kinetic AnalysesNucleotidyl Transfer Mechanism of Mismatched dNTP Incorporation by DNA Polymerase b by Structural and Kinetic Analyses
Structural highlights
FunctionDPOLB_RAT 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. 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 PubMedUnderstanding how DNA polymerases control fidelity requires elucidation of the mechanisms of matched and mismatched dNTP incorporations. Little is known about the latter because mismatched complexes do not crystallize readily. In this report, we employed small-angle X-ray scattering (SAXS) and structural modeling to probe the conformations of different intermediate states of mammalian DNA polymerase beta (Pol beta) in its wild-type and an error-prone variant, I260Q. Our structural results indicate that the mismatched ternary complex lies in-between the open and the closed forms, but more closely resembles the open form for WT and the closed form for I260Q. On the basis of molecular modeling, this over-stabilization of mismatched ternary complex of I260Q is likely caused by formation of a hydrogen bonding network between the side chains of Gln(260), Tyr(296), Glu(295) and Arg(258), freeing up Asp(192) to coordinate MgdNTP. These results argue against recent reports suggesting that mismatched dNTP incorporations follow a conformational path distinctly different from that of matched dNTP incorporation, or that its conformational closing is a major contributor to fidelity. Mismatched dNTP incorporation by DNA polymerase beta does not proceed via globally different conformational pathways.,Tang KH, Niebuhr M, Tung CS, Chan HC, Chou CC, Tsai MD Nucleic Acids Res. 2008 May;36(9):2948-57. Epub 2008 Apr 2. PMID:18385153[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||