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4tus

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==Human DNA polymerase beta inserting dCMPNPP opposite the 5'G of cisplatin crosslinked Gs (Pt-GG2) WITH MANGANESE IN THE ACTIVE SITE.==
==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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<StructureSection load='4tus' size='340' side='right' caption='[[4tus]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
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<StructureSection load='4tus' size='340' side='right'caption='[[4tus]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<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>
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<table><tr><td colspan='2'>[[4tus]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=4TUS FirstGlance]. <br>
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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=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.42&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tup|4tup]], [[4tuq|4tuq]], [[4tur|4tur]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4tus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tus OCA], [https://pdbe.org/4tus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tus RCSB], [https://www.ebi.ac.uk/pdbsum/4tus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tus ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/DPOLB_HUMAN 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.<ref>PMID:9207062</ref> <ref>PMID:9572863</ref> <ref>PMID:11805079</ref> <ref>PMID:21362556</ref>
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[https://www.uniprot.org/uniprot/DPOLB_HUMAN 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.<ref>PMID:9207062</ref> <ref>PMID:9572863</ref> <ref>PMID:11805079</ref> <ref>PMID:21362556</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Koag, M C]]
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[[Category: Homo sapiens]]
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[[Category: Lee, S]]
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[[Category: Large Structures]]
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[[Category: Dna polymerase]]
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[[Category: Koag MC]]
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[[Category: Lyase-dna complex]]
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[[Category: Lee S]]
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[[Category: Transferase]]
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Current revision

Human DNA polymerase beta inserting dCMPNPP opposite the 5'G of cisplatin crosslinked Gs (Pt-GG2) WITH MANGANESE IN THE ACTIVE SITE.

PDB ID 4tus

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