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6bel

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Revision as of 08:49, 11 November 2020

Ternary complex crystal structure of DNA polymerase Beta with R-isomer of beta-gamma-CHF-dCTP

Structural highlights

6bel is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
NonStd Res:
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

We report high-resolution crystal structures of DNA polymerase (pol) beta in ternary complex with a panel of incoming dNTPs carrying acidity-modified 5'-triphosphate groups. These novel dNTP analogues have a variety of halomethylene substitutions replacing the bridging oxygen between Pbeta and Pgamma of the incoming dNTP, whereas other analogues have alkaline substitutions at the bridging oxygen. Use of these analogues allows the first systematic comparison of effects of 5'-triphosphate acidity modification on active site structures and the rate constant of DNA synthesis. These ternary complex structures with incoming dATP, TTP and dCTP analogues reveal the enzyme's active site is not grossly altered by the acidity modifications of the triphosphate group. Yet, with analogues of all three incoming dNTP bases, subtle structural differences are apparent in interactions around the nascent base pair and at the guanidinium groups of active site arginine residues. These results are important in understanding how acidity modification of the incoming dNTP's 5'-triphosphate can influence DNA polymerase activity and the significance of interactions at arginines 183 and 149 in the active site.

Mapping functional substrate-enzyme interactions in the pol beta active site through chemical biology: Structural responses to acidity modification of incoming dNTPs.,Batra VK, Oertell K, Beard WA, Kashemirov BA, McKenna CE, Goodman MF, Wilson SH Biochemistry. 2018 Jun 6. doi: 10.1021/acs.biochem.8b00418. PMID:29874056^[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
↑ Batra VK, Oertell K, Beard WA, Kashemirov BA, McKenna CE, Goodman MF, Wilson SH. Mapping functional substrate-enzyme interactions in the pol beta active site through chemical biology: Structural responses to acidity modification of incoming dNTPs. Biochemistry. 2018 Jun 6. doi: 10.1021/acs.biochem.8b00418. PMID:29874056 doi:http://dx.doi.org/10.1021/acs.biochem.8b00418

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/6bel"

@@ Line 1: / Line 1: @@
 ==Ternary complex crystal structure of DNA polymerase Beta with R-isomer of beta-gamma-CHF-dCTP==
-<StructureSection load='6bel' size='340' side='right' caption='[[6bel]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='6bel' size='340' side='right'caption='[[6bel]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6bel]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BEL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BEL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6bel]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BEL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BEL 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=F3C:2-deoxy-5-O-[(R)-{[(R)-[(R)-fluoro(phosphono)methyl](hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl]cytidine'>F3C</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=F3C:2-deoxy-5-O-[(R)-{[(R)-[(R)-fluoro(phosphono)methyl](hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl]cytidine'>F3C</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2DA:2,3-DIDEOXYADENOSINE-5-MONOPHOSPHATE'>2DA</scene></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=6bel FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bel OCA], [http://pdbe.org/6bel PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bel RCSB], [http://www.ebi.ac.uk/pdbsum/6bel PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bel ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6bel FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bel OCA], [http://pdbe.org/6bel PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bel RCSB], [http://www.ebi.ac.uk/pdbsum/6bel PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bel ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6bel" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Batra, V K]]
 [[Category: Wilson, S H]]

6bel

From Proteopedia

Revision as of 08:49, 11 November 2020

Ternary complex crystal structure of DNA polymerase Beta with R-isomer of beta-gamma-CHF-dCTP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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