4o5k: Difference between revisions
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==Structure of human DNA polymerase complexed with N7MG in the template base paired with incoming non-hydrolyzable CTP== | ==Structure of human DNA polymerase complexed with N7MG in the template base paired with incoming non-hydrolyzable CTP== | ||
<StructureSection load='4o5k' size='340' side='right' caption='[[4o5k]], [[Resolution|resolution]] 2.06Å' scene=''> | <StructureSection load='4o5k' size='340' side='right' caption='[[4o5k]], [[Resolution|resolution]] 2.06Å' scene=''> | ||
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMG:2-AMINO-9-(2-DEOXY-2-FLUORO-5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-7-METHYL-6-OXO-6,9-DIHYDRO-1H-PURIN-7-IUM'>FMG</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMG:2-AMINO-9-(2-DEOXY-2-FLUORO-5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-7-METHYL-6-OXO-6,9-DIHYDRO-1H-PURIN-7-IUM'>FMG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3isb|3isb]], [[1bpx|1bpx]], [[4o5c|4o5c]], [[4o5e|4o5e]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3isb|3isb]], [[1bpx|1bpx]], [[4o5c|4o5c]], [[4o5e|4o5e]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o5k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o5k RCSB], [http://www.ebi.ac.uk/pdbsum/4o5k PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o5k OCA], [http://pdbe.org/4o5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o5k RCSB], [http://www.ebi.ac.uk/pdbsum/4o5k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o5k ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4o5k" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Revision as of 20:23, 9 March 2017
Structure of human DNA polymerase complexed with N7MG in the template base paired with incoming non-hydrolyzable CTPStructure of human DNA polymerase complexed with N7MG in the template base paired with incoming non-hydrolyzable CTP
Structural highlights
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.[1] [2] [3] [4] Publication Abstract from PubMedN7-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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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