4ub2: Difference between revisions
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==DNA polymerase beta product complex with a templating cytosine and 8-oxodGMP, 120 s== | ==DNA polymerase beta product complex with a templating cytosine and 8-oxodGMP, 120 s== | ||
<StructureSection load='4ub2' size='340' side='right' caption='[[4ub2]], [[Resolution|resolution]] 2.51Å' scene=''> | <StructureSection load='4ub2' size='340' side='right' caption='[[4ub2]], [[Resolution|resolution]] 2.51Å' scene=''> | ||
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uaw|4uaw]], [[4uay|4uay]], [[4uaz|4uaz]], [[4ub1|4ub1]], [[4ub3|4ub3]], [[4ub4|4ub4]], [[4ub5|4ub5]], [[4ubb|4ubb]], [[4ubc|4ubc]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uaw|4uaw]], [[4uay|4uay]], [[4uaz|4uaz]], [[4ub1|4ub1]], [[4ub3|4ub3]], [[4ub4|4ub4]], [[4ub5|4ub5]], [[4ubb|4ubb]], [[4ubc|4ubc]]</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=4ub2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ub2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ub2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ub2 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=4ub2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ub2 OCA], [http://pdbe.org/4ub2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ub2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ub2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ub2 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 4ub2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA polymerase|DNA polymerase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 12:53, 11 August 2016
DNA polymerase beta product complex with a templating cytosine and 8-oxodGMP, 120 sDNA polymerase beta product complex with a templating cytosine and 8-oxodGMP, 120 s
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 PubMedOxidative stress promotes genomic instability and human diseases. A common oxidized nucleoside is 8-oxo-7,8-dihydro-2'-deoxyguanosine, which is found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP). Nucleotide pools are especially vulnerable to oxidative damage. Therefore cells encode an enzyme (MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival and to modulate Escherichia coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner. How polymerases discriminate between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics. Even with cellular sanitizing activities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis. This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn) uses its Hoogsteen edge to base pair with adenine. Here we use time-lapse crystallography to follow 8-oxo-dGTP insertion opposite adenine or cytosine with human pol beta, to reveal that insertion is accommodated in either the syn- or anti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen-bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxo-dGTP uses charge modulation during insertion that can lead to a blocked DNA repair intermediate. Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide.,Freudenthal BD, Beard WA, Perera L, Shock DD, Kim T, Schlick T, Wilson SH Nature. 2014 Nov 17. doi: 10.1038/nature13886. PMID:25409153[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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