View source for 8vfd


==Ternary DNA Polymerase Beta bound to DNA containing template FapydG incoming TTP analog==
<StructureSection load='8vfd' size='340' side='right'caption='[[8vfd]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vfd]] 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=8VFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VFD 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8NI:N-[(5S)-2-amino-5-formamido-6-oxo-5,6-dihydropyrimidin-4-yl]-2-deoxy-5-O-phosphono-beta-D-erythro-pentofuranosylamine'>8NI</scene>, <scene name='pdbligand=A1ACD:1-{2-deoxy-5-O-[(R)-hydroxy{[(S)-hydroxy(phosphonooxy)phosphoryl]methyl}phosphoryl]-beta-D-threo-pentofuranosyl}-5-methylpyrimidine-2,4(1H,3H)-dione'>A1ACD</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=8vfd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vfd OCA], [https://pdbe.org/8vfd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vfd RCSB], [https://www.ebi.ac.uk/pdbsum/8vfd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vfd 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 ==
N6-(2-deoxy-alpha,beta-d-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy*dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). Fapy*dG preferentially gives rise to G --&gt; T transversions and G --&gt; A transitions. However, the molecular basis by which Fapy*dG is processed by DNA polymerases during this mutagenic process remains poorly understood. To address this we investigated how DNA polymerase beta (Pol beta), a model mammalian polymerase, bypasses a templating Fapy*dG, inserts Fapy*dGTP, and extends from Fapy*dG at the primer terminus. When Fapy*dG is present in the template, Pol beta incorporates TMP less efficiently than either dCMP or dAMP. Kinetic analysis revealed that Fapy*dGTP is a poor substrate but is incorporated approximately 3-times more efficiently opposite dA than dC. Extension from Fapy*dG at the 3'-terminus of a nascent primer is inefficient due to the primer terminus being poorly positioned for catalysis. Together these data indicate that mutagenic bypass of Fapy*dG is likely to be the source of the mutagenic effects of the lesion and not Fapy*dGTP. These experiments increase our understanding of the promutagenic effects of Fapy*dG.

Biochemical and structural characterization of Fapy*dG replication by Human DNA polymerase beta.,Gao S, Oden PN, Ryan BJ, Yang H, Freudenthal BD, Greenberg MM Nucleic Acids Res. 2024 Apr 18:gkae277. doi: 10.1093/nar/gkae277. PMID:38634780<ref>PMID:38634780</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vfd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Freudenthal BD]]
[[Category: Oden PN]]
[[Category: Ryan BJ]]