6e3v: Difference between revisions

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-'''Unreleased structure'''
-The entry 6e3v is ON HOLD  until Paper Publication
+==Structure of human DNA polymerase beta complexed with 8OA in the template base paired with incoming non-hydrolyzable TTP==
+<StructureSection load='6e3v' size='340' side='right'caption='[[6e3v]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6e3v]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E3V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E3V FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1FZ:5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]THYMIDINE'>1FZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=A38:8-OXY+DEOXYADENOSINE-5-MONOPHOSPHATE'>A38</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xk3|4xk3]], [[4xk6|4xk6]], [[4xk7|4xk7]]</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=6e3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e3v OCA], [http://pdbe.org/6e3v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e3v RCSB], [http://www.ebi.ac.uk/pdbsum/6e3v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e3v ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Reactive oxygen species attack DNA to produce 7,8-dihyro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as major lesions. The structural basis for the mutagenicity of oxoG, which induces G to T mutations, is well understood. However, the structural basis for the mutagenic potential of oxoA, which induces A to C mutations, remains poorly understood. To gain insight into oxoA-induced mutagenesis, we conducted kinetic studies of human DNA polymerases beta and eta replicating across oxoA and structural studies of polbeta incorporating dTTP/dGTP opposite oxoA. While poleta readily bypassed oxoA, it incorporated dGTP opposite oxoA with a catalytic specificity comparable to that of correct insertion, underscoring the promutagenic nature of the major oxidative adenine lesion. Poleta and polbeta incorporated dGTP opposite oxoA approximately 170-fold and approximately 100-fold more efficiently than that opposite dA, respectively, indicating that the 8-oxo moiety greatly facilitated error-prone replication. Crystal structures of polbeta showed that, when paired with an incoming dTTP, the templating oxoA adopted an anti conformation and formed Watson-Crick base pair. When paired with dGTP, oxoA adopted a syn conformation and formed a Hoogsteen base pair with Watson-Crick-like geometry, highlighting the dual-coding potential of oxoA. The templating oxoA was stabilized by Lys280-mediated stacking and hydrogen bonds. Overall, these results provide insight into the mutagenic potential and dual-coding nature of the major oxidative adenine lesion.
-Authors: Koag, M.-C., Lee, S.
+Mutagenic Replication of the Major Oxidative Adenine Lesion 7,8-Dihydro-8-oxoadenine by Human DNA Polymerases.,Koag MC, Jung H, Lee S J Am Chem Soc. 2019 Mar 20;141(11):4584-4596. doi: 10.1021/jacs.8b08551. Epub, 2019 Mar 7. PMID:30817143<ref>PMID:30817143</ref>
-Description: Structure of human DNA polymerase beta complexed with 8OA in the template base paired with incoming non-hydrolyzable TTP
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Koag, M.-C]]
+<div class="pdbe-citations 6e3v" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Koag, M C]]
 [[Category: Lee, S]]
+[[Category: Dna binding protein]]
+[[Category: Dna binding protein-dna complex]]
+[[Category: Dna polymerase]]
+[[Category: Transferase-dna complex]]