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5v1p

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Revision as of 09:26, 1 January 2020

DNA polymerase beta substrate complex with 8-oxoG:C at the primer terminus and incoming dCTP analog

Structural highlights

5v1p 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:	5vif, 5vig, 5vih, 5vii, 5vij, 5vin, 5vio, 5vir
Gene:	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

The oxidized nucleotide, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxoG), is one of the most abundant DNA lesions. 8-oxoG plays a major role in tumorigenesis and human disease. Biological consequences of 8-oxoG are mediated in part by its insertion into the genome, making it essential to understand how DNA polymerases handle 8-oxoG. Insertion of 8-oxoG is mutagenic when opposite adenine but not when opposite cytosine. However, either result leads to DNA damage at the primer terminus (3-end) during the succeeding insertion event. Extension from DNA damage at primer termini remains poorly understood. Using kinetics and time-lapse crystallography, we evaluated how a model DNA polymerase, human polymerase beta, accommodates 8-oxoG at the primer terminus opposite cytosine and adenine. Notably, extension from the mutagenic base pair is favored over the non-mutagenic base pair. When 8-oxoG is at the primer terminus opposite cytosine, DNA centric changes lead to a clash between O8 of 8-oxoG and the phosphate backbone. Changes in the extension reaction resulting from the altered active site provide evidence for a stabilizing interaction between Arg254 and Asp256 that serves an important role during DNA synthesis reactions. These results provide novel insights into the impact of damage at the primer terminus on genomic stability and DNA synthesis.

Capturing a mammalian DNA polymerase extending from an oxidized nucleotide.,Whitaker AM, Smith MR, Schaich MA, Freudenthal BD Nucleic Acids Res. 2017 Apr 26. doi: 10.1093/nar/gkx293. PMID:28449123^[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
↑ Whitaker AM, Smith MR, Schaich MA, Freudenthal BD. Capturing a mammalian DNA polymerase extending from an oxidized nucleotide. Nucleic Acids Res. 2017 Apr 26. doi: 10.1093/nar/gkx293. PMID:28449123 doi:http://dx.doi.org/10.1093/nar/gkx293

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/5v1p"

@@ Line 1: / Line 1: @@
 ==DNA polymerase beta substrate complex with 8-oxoG:C at the primer terminus and incoming dCTP analog==
-<StructureSection load='5v1p' size='340' side='right' caption='[[5v1p]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
+<StructureSection load='5v1p' size='340' side='right'caption='[[5v1p]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5v1p]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V1P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V1P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5v1p]] 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=5V1P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V1P FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XC5:2-DEOXY-5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]METHYL}PHOSPHORYL]CYTIDINE'>XC5</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">[[5vif|5vif]], [[5vig|5vig]], [[5vih|5vih]], [[5vii|5vii]], [[5vij|5vij]], [[5vin|5vin]], [[5vio|5vio]], [[5vir|5vir]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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=5v1p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v1p OCA], [http://pdbe.org/5v1p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v1p RCSB], [http://www.ebi.ac.uk/pdbsum/5v1p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v1p ProSAT]</span></td></tr>
 </table>
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5v1p" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Freudenthal, B D]]
 [[Category: Schaich, M A]]

5v1p

From Proteopedia

Revision as of 09:26, 1 January 2020

DNA polymerase beta substrate complex with 8-oxoG:C at the primer terminus and incoming dCTP analog

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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