7s9k
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Crystal Structure of DNA Polymerase Beta with Fapy-dG base-paired with a dA== |
| - | <StructureSection load='7s9k' size='340' side='right'caption='[[7s9k]]' scene=''> | + | <StructureSection load='7s9k' size='340' side='right'caption='[[7s9k]], [[Resolution|resolution]] 1.97Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7s9k]] 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=7S9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S9K FirstGlance]. <br> |
| - | </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=7s9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s9k OCA], [https://pdbe.org/7s9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s9k RCSB], [https://www.ebi.ac.uk/pdbsum/7s9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s9k ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7s9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s9k OCA], [https://pdbe.org/7s9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s9k RCSB], [https://www.ebi.ac.uk/pdbsum/7s9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s9k ProSAT]</span></td></tr> | ||
</table> | </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-formamid o pyrimidine (Fapy*dG) is a prevalent form of genomic DNA damage. Fapy*dG is formed in greater amounts under anoxic conditions than the well-studied, chemically related 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodGuo). Fapy*dG is more mutagenic in mammalian cells than 8-oxodGuo. A distinctive property of Fapy*dG is facile epimerization, but prior works with Fapy*dG analogues have precluded determining its effect on chemistry. We present crystallographic characterization of natural Fapy*dG in duplex DNA and as the template base for DNA polymerase beta (Pol beta). Fapy*dG adopts the beta-anomer when base paired with cytosine but exists as a mixture of alpha- and beta-anomers when promutagenically base paired with adenine. Rotation about the bond between the glycosidic nitrogen atom and the pyrimidine ring is also affected by the opposing nucleotide. Sodium cyanoborohydride soaking experiments trap the ring-opened Fapy*dG, demonstrating that ring opening and epimerization occur in the crystalline state. Ring opening and epimerization are facilitated by propitious water molecules that are observed in the structures. Determination of Fapy*dG mutagenicity in wild type and Pol beta knockdown HEK 293T cells indicates that Pol beta contributes to G --> T transversions but also suppresses G --> A transitions. Complementary kinetic studies have determined that Fapy*dG promotes mutagenesis by decreasing the catalytic efficiency of dCMP insertion opposite Fapy*dG, thus reducing polymerase fidelity. Kinetic studies have determined that dCMP incorporation opposite the beta-anomer is approximately 90 times faster than the alpha-anomer. This research identifies the importance of anomer dynamics, a feature unique to formamidopyrimidines, when considering the incorporation of nucleotides opposite Fapy*dG and potentially the repair of this structurally unusual lesion. | ||
| + | |||
| + | Structural Dynamics of a Common Mutagenic Oxidative DNA Lesion in Duplex DNA and during DNA Replication.,Ryan BJ, Yang H, Bacurio JHT, Smith MR, Basu AK, Greenberg MM, Freudenthal BD J Am Chem Soc. 2022 May 11;144(18):8054-8065. doi: 10.1021/jacs.2c00193. Epub, 2022 May 2. PMID:35499923<ref>PMID:35499923</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7s9k" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Synthetic construct]] |
| + | [[Category: Freudenthal BD]] | ||
| + | [[Category: Ryan BJ]] | ||
Revision as of 03:15, 8 September 2022
Crystal Structure of DNA Polymerase Beta with Fapy-dG base-paired with a dA
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