6e3v: Difference between revisions
New page: '''Unreleased structure''' The entry 6e3v is ON HOLD Authors: Koag, M.-C., Lee, S. Description: Structure of human DNA polymerase beta complexed with 8OA in the template base paired wi... |
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The | ==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]] 1.96Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6e3v]] 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=6E3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E3V 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]] 1.96Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1FZ:5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]THYMIDINE'>1FZ</scene>, <scene name='pdbligand=A38:8-OXY+DEOXYADENOSINE-5-MONOPHOSPHATE'>A38</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6e3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e3v OCA], [https://pdbe.org/6e3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e3v RCSB], [https://www.ebi.ac.uk/pdbsum/6e3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e3v 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 == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6e3v" style="background-color:#fffaf0;"></div> | ||
[[Category: Koag | |||
==See Also== | |||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Koag M-C]] | |||
[[Category: Lee S]] | |||
Latest revision as of 09:18, 11 October 2023
Structure of human DNA polymerase beta complexed with 8OA in the template base paired with incoming non-hydrolyzable TTPStructure of human DNA polymerase beta complexed with 8OA in the template base paired with incoming non-hydrolyzable TTP
Structural highlights
FunctionDPOLB_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.[1] [2] [3] [4] Publication Abstract from PubMedReactive 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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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