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4p2h
From Proteopedia
(Difference between revisions)
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p2h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p2h RCSB], [http://www.ebi.ac.uk/pdbsum/4p2h PDBsum]</span></td></tr> | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p2h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p2h RCSB], [http://www.ebi.ac.uk/pdbsum/4p2h PDBsum]</span></td></tr> | ||
<table> | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | N7-Methyl-2'-deoxyguanosine (m7dG) is the predominant lesion formed by methylating agents. A systematic investigation on the effect of m7dG on DNA replication has been difficult due to the chemical instability of m7dG. To gain insights into the m7dG effect, we employed a 2'-fluorine-mediated transition-state destabilzation strategy. Specifically, we determined kinetic parameters for dCTP insertion opposite a chemically stable m7dG analogue, 2'-fluoro-m7dG (Fm7dG), by human DNA polymerase beta (polbeta) and solved three X-ray structures of polbeta in complex with the templating Fm7dG paired with incoming dCTP or dTTP analogues. The kinetic studies reveal that the templating Fm7dG slows polbeta catalysis approximately 300-fold, suggesting that m7dG in genomic DNA may impede replication by some DNA polymerases. The structural analysis reveals that Fm7dG forms a canonical Watson-Crick base pair with dCTP, but metal ion coordination is suboptimal for catalysis in the polbeta-Fm7dG:dCTP complex, which partially explains the slow insertion of dCTP opposite Fm7dG by polbeta. In addition, the polbeta-Fm7dG:dTTP structure shows open protein conformations and staggered base pair conformations, indicating that N7-methylation of dG does not promote a promutagenic replication. Overall, the first systematic studies on the effect of m7dG on DNA replication reveal that polbeta catalysis across m7dG is slow, yet highly accurate. | ||
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| + | Transition-state destabilization reveals how human DNA polymerase beta proceeds across the chemically unstable lesion N7-methylguanine.,Koag MC, Kou Y, Ouzon-Shubeita H, Lee S Nucleic Acids Res. 2014 Jun 25. pii: gku554. PMID:24966350<ref>PMID:24966350</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 06:21, 9 July 2014
Structure of human DNA polymerase complexed with N7MG in the template opposite to incoming non-hydrolyzable TTP with manganese in the active site
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