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4rq0

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Revision as of 10:30, 1 May 2019

Human DNA Polymerase Beta With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine (8-oxoG)and dCTP soaked with MgCl2 for 80 s

Structural highlights

4rq0 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
NonStd Res:
Related:	4rpx, 4rpy, 4rpz, 4rq1, 4rq2, 4rq3, 4rq4, 4rq5, 4rq6, 4rq7, 4rq8
Gene:	POL B, POLB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), is highly mutagenic in vivo due to its anti-conformation forming a Watson-Crick base pair with correct deoxycytidine 5'-triphosphate (dCTP) and its syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine 5'-triphosphate (dATP). Here, we utilized time-resolved X-ray crystallography to follow 8-oxoG bypass by human DNA polymerase beta (hPolbeta). In the 12 solved structures, both Watson-Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen (syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained throughout the chemical reaction. Additionally, a third Mg2+ appeared during the process of phosphodiester bond formation and was located between the reacting alpha- and beta-phosphates of the dNTP, suggesting its role in stabilizing reaction intermediates. After phosphodiester bond formation, hPolbeta reopened its conformation, pyrophosphate was released, and the newly incorporated primer 3'-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These structures provide the first real-time pictures, to our knowledge, of how a polymerase correctly and incorrectly bypasses a DNA lesion.

Viewing Human DNA Polymerase beta Faithfully and Unfaithfully Bypass an Oxidative Lesion by Time-Dependent Crystallography.,Vyas R, Reed AJ, Tokarsky EJ, Suo Z J Am Chem Soc. 2015 Apr 9. PMID:25825995^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Vyas R, Reed AJ, Tokarsky EJ, Suo Z. Viewing Human DNA Polymerase beta Faithfully and Unfaithfully Bypass an Oxidative Lesion by Time-Dependent Crystallography. J Am Chem Soc. 2015 Apr 9. PMID:25825995 doi:http://dx.doi.org/10.1021/jacs.5b02109

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rq0"

@@ Line 1: / Line 1: @@
 ==Human DNA Polymerase Beta With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine (8-oxoG)and dCTP soaked with MgCl2 for 80 s==
-<StructureSection load='4rq0' size='340' side='right' caption='[[4rq0]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='4rq0' size='340' side='right'caption='[[4rq0]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4rq0]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RQ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RQ0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4rq0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RQ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RQ0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PPV:PYROPHOSPHATE'>PPV</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rpx|4rpx]], [[4rpy|4rpy]], [[4rpz|4rpz]], [[4rq1|4rq1]], [[4rq2|4rq2]], [[4rq3|4rq3]], [[4rq4|4rq4]], [[4rq5|4rq5]], [[4rq6|4rq6]], [[4rq7|4rq7]], [[4rq8|4rq8]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POL B, POLB ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rq0 OCA], [http://pdbe.org/4rq0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rq0 RCSB], [http://www.ebi.ac.uk/pdbsum/4rq0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rq0 ProSAT]</span></td></tr>
 </table>
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 4rq0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase|DNA polymerase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Suo, Z]]
 [[Category: Vyas, R]]

4rq0

From Proteopedia

Revision as of 10:30, 1 May 2019

Human DNA Polymerase Beta With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine (8-oxoG)and dCTP soaked with MgCl2 for 80 s

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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