4tus
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4tus]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TUS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TUS FirstGlance]. <br> | <table><tr><td colspan='2'>[[4tus]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TUS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TUS FirstGlance]. <br> | ||
| - | </td></tr><tr><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=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>< | + | </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=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tup|4tup]], [[4tuq|4tuq]], [[4tur|4tur]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tup|4tup]], [[4tuq|4tuq]], [[4tur|4tur]]</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=4tus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tus OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tus RCSB], [http://www.ebi.ac.uk/pdbsum/4tus 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=4tus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tus OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tus RCSB], [http://www.ebi.ac.uk/pdbsum/4tus PDBsum]</span></td></tr> |
| - | <table> | + | </table> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human 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. | ||
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| + | 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<ref>PMID:25237188</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 08:46, 20 October 2014
Human DNA polymerase beta inserting dCMPNPP opposite the 5'G of cisplatin crosslinked Gs (Pt-GG2) WITH MANGANESE IN THE ACTIVE SITE.
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