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5bpc

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==DNA polymerase beta ternary complex with a templating 5ClC and incoming dATP analog==
==DNA polymerase beta ternary complex with a templating 5ClC and incoming dATP analog==
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<StructureSection load='5bpc' size='340' side='right' caption='[[5bpc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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<StructureSection load='5bpc' size='340' side='right'caption='[[5bpc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5bpc]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BPC FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5bpc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BPC 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=F2A:2-DEOXY-5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]METHYL}PHOSPHORYL]ADENOSINE'>F2A</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&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=4U3:5-CHLORO-2-DEOXYCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>4U3</scene></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=4U3:5-CHLORO-2-DEOXYCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>4U3</scene>, <scene name='pdbligand=F2A:2-DEOXY-5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]METHYL}PHOSPHORYL]ADENOSINE'>F2A</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=5bpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bpc RCSB], [http://www.ebi.ac.uk/pdbsum/5bpc 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=5bpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpc OCA], [https://pdbe.org/5bpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bpc RCSB], [https://www.ebi.ac.uk/pdbsum/5bpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpc 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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During chronic inflammation, neutrophil-secreted hypochlorous acid can damage nearby cells inducing the genomic accumulation of 5-chlorocytosine (5ClC), a known inflammation biomarker. Although 5ClC has been shown to promote epigenetic changes, it has been unknown heretofore if 5ClC directly perpetrates a mutagenic outcome within the cell. The present work shows that 5ClC is intrinsically mutagenic, both in vitro and, at a level of a single molecule per cell, in vivo. Using biochemical and genetic approaches, we have quantified the mutagenic and toxic properties of 5ClC, showing that this lesion caused C--&gt;T transitions at frequencies ranging from 3-9% depending on the polymerase traversing the lesion. X-ray crystallographic studies provided a molecular basis for the mutagenicity of 5ClC; a snapshot of human polymerase beta replicating across a primed 5ClC-containing template uncovered 5ClC engaged in a nascent base pair with an incoming dATP analog. Accommodation of the chlorine substituent in the template major groove enabled a unique interaction between 5ClC and the incoming dATP, which would facilitate mutagenic lesion bypass. The type of mutation induced by 5ClC, the C--&gt;T transition, has been previously shown to occur in substantial amounts both in tissues under inflammatory stress and in the genomes of many inflammation-associated cancers. In fact, many sequence-specific mutational signatures uncovered in sequenced cancer genomes feature C--&gt;T mutations. Therefore, the mutagenic ability of 5ClC documented in the present study may constitute a direct functional link between chronic inflammation and the genetic changes that enable and promote malignant transformation.
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Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer.,Fedeles BI, Freudenthal BD, Yau E, Singh V, Chang SC, Li D, Delaney JC, Wilson SH, Essigmann JM Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):E4571-80. doi:, 10.1073/pnas.1507709112. Epub 2015 Aug 4. PMID:26243878<ref>PMID:26243878</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: Freudenthal, B D]]
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[[Category: Homo sapiens]]
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[[Category: Wilson, S H]]
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[[Category: Large Structures]]
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[[Category: Ligase-dna complex]]
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[[Category: Synthetic construct]]
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[[Category: Lyase/dna]]
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[[Category: Freudenthal BD]]
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[[Category: Transferase]]
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[[Category: Wilson SH]]

Current revision

DNA polymerase beta ternary complex with a templating 5ClC and incoming dATP analog

PDB ID 5bpc

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