5tbc
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==PRECATALYTIC TERNARY COMPLEX OF HUMAN DNA POLYMERASE BETA WITH GAPPED DNA SUBSTRATE, INCORPORATED (-)3TC-MP AND AN ANOTHER INCOMING (-)3TC-TP NUCLEOTIDE.== | |
| + | <StructureSection load='5tbc' size='340' side='right' caption='[[5tbc]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5tbc]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TBC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TBC FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1RZ:[[(2R,5S)-5-(4-AZANYL-2-OXIDANYLIDENE-PYRIMIDIN-1-YL)-1,3-OXATHIOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]+PHOSPHONO+HYDROGEN+PHOSPHATE'>1RZ</scene>, <scene name='pdbligand=42E:[(2R,5S)-5-(4-AMINO-2-OXOPYRIMIDIN-1(2H)-YL)-1,3-OXATHIOLAN-2-YL]METHYL+DIHYDROGEN+PHOSPHATE'>42E</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tba|5tba]], [[5tb8|5tb8]], [[5tbb|5tbb]], [[5tb9|5tb9]]</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=5tbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tbc OCA], [http://pdbe.org/5tbc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tbc RCSB], [http://www.ebi.ac.uk/pdbsum/5tbc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tbc 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 == | ||
| + | DNA polymerases are essential enzymes that faithfully and efficiently replicate genomic information.1-3 The mechanism of nucleotide incorporation by DNA polymerases has been extensively studied structurally and kinetically, but several key steps following phosphodiester bond formation remain structurally uncharacterized due to utilization of natural nucleotides. It is thought that the release of pyrophosphate (PPi) triggers reverse conformational changes in a polymerase in order to complete a full catalytic cycle as well as prepare for DNA translocation and subsequent incorporation events. Here, by using the triphosphates of chain-terminating antiviral drugs lamivudine ((-)3TC-TP) and emtricitabine ((-)FTC-TP), we structurally reveal the correct sequence of post-chemistry steps during nucleotide incorporation by human DNA polymerase beta (hPolbeta) and provide a structural basis for PPi release. These post-catalytic structures reveal hPolbeta in an open conformation with PPi bound in the active site, thereby strongly suggesting that the reverse conformational changes occur prior to PPi release. The results also help to refine the role of the newly discovered third divalent metal ion for DNA polymerase-catalyzed nucleotide incorporation. Furthermore, a post-chemistry structure of hPolbeta in the open conformation, following incorporation of (-)3TC-MP, with a second (-)3TC-TP molecule bound to the active site in the absence of PPi, suggests that nucleotide binding stimulates PPi dissociation and occurs before polymerase translocation. Our structural characterization defines the order of the elusive post-chemistry steps in the canonical mechanism of a DNA polymerase. | ||
| - | + | Structural Insights into the Post-Chemistry Steps of Nucleotide Incorporation Catalyzed by a DNA Polymerase.,Reed AJ, Vyas R, Raper AT, Suo Z J Am Chem Soc. 2017 Jan 11;139(1):465-471. doi: 10.1021/jacs.6b11258. Epub 2016, Dec 27. PMID:27959534<ref>PMID:27959534</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 5tbc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Suo, Z]] | [[Category: Suo, Z]] | ||
[[Category: Vyas, R]] | [[Category: Vyas, R]] | ||
| + | [[Category: Dna polymerase beta]] | ||
| + | [[Category: Pol beta]] | ||
| + | [[Category: Transferase-dna complex]] | ||
| + | [[Category: X-family]] | ||
Revision as of 16:38, 18 January 2017
PRECATALYTIC TERNARY COMPLEX OF HUMAN DNA POLYMERASE BETA WITH GAPPED DNA SUBSTRATE, INCORPORATED (-)3TC-MP AND AN ANOTHER INCOMING (-)3TC-TP NUCLEOTIDE.
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