4tuq: Difference between revisions
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==Human DNA polymerase beta inserting dCMPNPP opposite GG template (GG0b).== | ==Human DNA polymerase beta inserting dCMPNPP opposite GG template (GG0b).== | ||
<StructureSection load='4tuq' size='340' side='right' caption='[[4tuq]], [[Resolution|resolution]] 2.37Å' scene=''> | <StructureSection load='4tuq' size='340' side='right' caption='[[4tuq]], [[Resolution|resolution]] 2.37Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tup|4tup]], [[4tur|4tur]], [[4tus|4tus]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tup|4tup]], [[4tur|4tur]], [[4tus|4tus]]</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=4tuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tuq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tuq RCSB], [http://www.ebi.ac.uk/pdbsum/4tuq 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=4tuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tuq OCA], [http://pdbe.org/4tuq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tuq RCSB], [http://www.ebi.ac.uk/pdbsum/4tuq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tuq 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 4tuq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA polymerase|DNA polymerase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 23:20, 4 August 2016
Human DNA polymerase beta inserting dCMPNPP opposite GG template (GG0b).Human DNA polymerase beta inserting dCMPNPP opposite GG template (GG0b).
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 PubMedHuman DNA polymerase beta (polbeta) has been suggested to play a role in cisplatin resistance, especially in polbeta-overexpressing cancer cells. Polbeta has been shown to accurately, albeit slowly bypass the cisplatin-1,2-d(GpG) (Pt-GG) intramolecular cross-link in vitro. Currently, the structural basis for the inefficient Pt-GG bypass mechanism of polbeta is unknown. To gain structural insights into the mechanism, we determined two ternary structures of polbeta incorporating dCTP opposite the templating Pt-GG lesion in the presence of the active-site Mg2+ or Mn2+. The Mg2+-bound structure shows that the bulky Pt-GG adduct is accommodated in the polbeta active site without any steric hindrance. In addition, both guanines of the Pt-GG lesion form Watson-Crick base pairing with the primer terminus dC and the incoming dCTP, providing the structural basis for the accurate bypass of the Pt-GG adduct by polbeta. The Mn2+-bound structure shows that polbeta adopts a catalytically sub-optimal semi-closed conformation during the insertion of dCTP opposite the templating Pt-GG, explaining the inefficient replication across the Pt-GG lesion by polbeta. Overall, our studies provide the first structural insights into the mechanism of the potential polbeta-mediated cisplatin resistance. Structural Basis for the Inefficient Nucleotide Incorporation Opposite Cisplatin-DNA Lesion by Human DNA Polymerase beta,Koag MC, Lai L, Lee S J Biol Chem. 2014 Sep 18. pii: jbc.M114.605451. PMID:25237188[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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