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| | <StructureSection load='3isc' size='340' side='right'caption='[[3isc]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3isc' size='340' side='right'caption='[[3isc]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3isc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ISC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ISC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3isc]] 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=3ISC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ISC FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</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"><div style='overflow: auto; max-height: 3em;'>[[1bpx|1bpx]], [[3isb|3isb]], [[3isd|3isd]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POLB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3isc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3isc OCA], [https://pdbe.org/3isc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3isc RCSB], [https://www.ebi.ac.uk/pdbsum/3isc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3isc ProSAT]</span></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=3isc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3isc OCA], [https://pdbe.org/3isc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3isc RCSB], [https://www.ebi.ac.uk/pdbsum/3isc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3isc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3isc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3isc" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Batra, V K]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Beard, W A]] | + | [[Category: Batra VK]] |
| - | [[Category: Pedersen, L C]] | + | [[Category: Beard WA]] |
| - | [[Category: Shock, D D]] | + | [[Category: Pedersen LC]] |
| - | [[Category: Wilson, S H]] | + | [[Category: Shock DD]] |
| - | [[Category: Abasic site]] | + | [[Category: Wilson SH]] |
| - | [[Category: Binary complex]]
| + | |
| - | [[Category: Dna damage]]
| + | |
| - | [[Category: Dna polymerase beta]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Dna replication]]
| + | |
| - | [[Category: Dna synthesis]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Dna-directed dna polymerase]]
| + | |
| - | [[Category: Gapped dna]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Magnesium]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Methylation]]
| + | |
| - | [[Category: Nucleotidyl transferase]]
| + | |
| - | [[Category: Nucleotidyltransferase]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Sodium]]
| + | |
| - | [[Category: Tetrahydrofuran]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-dna complex]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Apurinic/apyrimidinic (AP) sites are continuously generated in genomic DNA. Left unrepaired, AP sites represent noninstructional premutagenic lesions that are impediments to DNA synthesis. When DNA polymerases encounter an AP site, they generally insert dAMP. This preferential insertion is referred to as the A-rule. Crystallographic structures of DNA polymerase (pol) beta, a family X polymerase, with active site mismatched nascent base pairs indicate that the templating (i.e. coding) base is repositioned outside of the template binding pocket thereby diminishing interactions with the incorrect incoming nucleotide. This effectively produces an abasic site because the template pocket is devoid of an instructional base. However, the template pocket is not empty; an arginine residue (Arg-283) occupies the space vacated by the templating nucleotide. In this study, we analyze the kinetics of pol beta insertion opposite an AP site and show that the preferential incorporation of dAMP is lost with the R283A mutant. The crystallographic structures of pol beta bound to gapped DNA with an AP site analog (tertrahydrofuran) in the gap (binary complex) and with an incoming nonhydrolyzable dATP analog (ternary complex) were solved. These structures reveal that binding of the dATP analog induces a closed polymerase conformation, an unstable primer terminus, and an upstream shift of the templating residue even in the absence of a template base. Thus, dATP insertion opposite an abasic site and dATP misinsertions have common features.
DNA polymerase beta substrate specificity: side chain modulation of the "A-rule".,Beard WA, Shock DD, Batra VK, Pedersen LC, Wilson SH J Biol Chem. 2009 Nov 13;284(46):31680-9. Epub 2009 Sep 15. PMID:19759017[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bennett RA, Wilson DM 3rd, Wong D, Demple B. Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-9. PMID:9207062
- ↑ Matsumoto Y, Kim K, Katz DS, Feng JA. Catalytic center of DNA polymerase beta for excision of deoxyribose phosphate groups. Biochemistry. 1998 May 5;37(18):6456-64. PMID:9572863 doi:10.1021/bi9727545
- ↑ DeMott MS, Beyret E, Wong D, Bales BC, Hwang JT, Greenberg MM, Demple B. Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone. J Biol Chem. 2002 Mar 8;277(10):7637-40. Epub 2002 Jan 22. PMID:11805079 doi:10.1074/jbc.C100577200
- ↑ Parsons JL, Dianova II, Khoronenkova SV, Edelmann MJ, Kessler BM, Dianov GL. USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase beta. Mol Cell. 2011 Mar 4;41(5):609-15. doi: 10.1016/j.molcel.2011.02.016. PMID:21362556 doi:10.1016/j.molcel.2011.02.016
- ↑ Beard WA, Shock DD, Batra VK, Pedersen LC, Wilson SH. DNA polymerase beta substrate specificity: side chain modulation of the "A-rule". J Biol Chem. 2009 Nov 13;284(46):31680-9. Epub 2009 Sep 15. PMID:19759017 doi:10.1074/jbc.M109.029843
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