6dic
From Proteopedia
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- | '''Unreleased structure''' | ||
- | + | ==D276G DNA polymerase beta substrate complex with templating cytosine and incoming Fapy-dGTP analog== | |
+ | <StructureSection load='6dic' size='340' side='right'caption='[[6dic]], [[Resolution|resolution]] 1.99Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[6dic]] 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=6DIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DIC FirstGlance]. <br> | ||
+ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.992Å</td></tr> | ||
+ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GKS:1-[2-amino-5-(formylamino)-6-oxo-1,6-dihydropyrimidin-4-yl]-2,5-anhydro-1,3-dideoxy-6-O-[(R)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]oxy}phosphoryl]-D-ribo-hexitol'>GKS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
+ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6dic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dic OCA], [https://pdbe.org/6dic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dic RCSB], [https://www.ebi.ac.uk/pdbsum/6dic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dic ProSAT]</span></td></tr> | ||
+ | </table> | ||
+ | == Function == | ||
+ | [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> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | 4,6-Diamino-5-formamidopyrimidine (Fapy*dG) is an abundant form of oxidative DNA damage that is mutagenic and contributes to the pathogenesis of human disease. When Fapy*dG is in its nucleotide triphosphate form, Fapy*dGTP, it is inefficiently cleansed from the nucleotide pool by the responsible enzyme in Escherichia coli MutT and its mammalian homolog MTH1. Therefore, under oxidative stress conditions, Fapy*dGTP could become a pro-mutagenic substrate for insertion into the genome by DNA polymerases. Here, we evaluated insertion kinetics and high-resolution ternary complex crystal structures of a configurationally stable Fapy*dGTP analog, beta-C-Fapy*dGTP, with DNA polymerase beta. The crystallographic snapshots and kinetic data indicate that binding of beta-C-Fapy*dGTP impedes enzyme closure, thus hindering insertion. The structures reveal that an active site residue, Asp276, positions beta-C-Fapy*dGTP so that it distorts the geometry of critical catalytic atoms. Removal of this guardian side chain permits enzyme closure and increases the efficiency of beta-C-Fapy*dG insertion opposite dC. These results highlight the stringent requirements necessary to achieve a closed DNA polymerase active site poised for efficient nucleotide incorporation and illustrate how DNA polymerase beta has evolved to hinder Fapy*dGTP insertion. | ||
- | + | A guardian residue hinders insertion of a Fapy*dGTP analog by modulating the open-closed DNA polymerase transition.,Smith MR, Shock DD, Beard WA, Greenberg MM, Freudenthal BD, Wilson SH Nucleic Acids Res. 2019 Jan 16. pii: 5289696. doi: 10.1093/nar/gkz002. PMID:30649431<ref>PMID:30649431</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | [[Category: | + | </div> |
+ | <div class="pdbe-citations 6dic" style="background-color:#fffaf0;"></div> | ||
+ | |||
+ | ==See Also== | ||
+ | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | ||
+ | == References == | ||
+ | <references/> | ||
+ | __TOC__ | ||
+ | </StructureSection> | ||
+ | [[Category: Homo sapiens]] | ||
+ | [[Category: Large Structures]] | ||
+ | [[Category: Synthetic construct]] | ||
+ | [[Category: Beard WA]] | ||
+ | [[Category: Freudenthal BD]] | ||
+ | [[Category: Smith MR]] | ||
+ | [[Category: Wilson SH]] |
Current revision
D276G DNA polymerase beta substrate complex with templating cytosine and incoming Fapy-dGTP analog
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