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3jps

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Revision as of 08:35, 5 August 2016

Ternary complex of DNA polymerase beta with a dideoxy terminated primer and 2'-deoxyguanosine 5'-beta, gamma-fluoro methyl methylene triphosphate

Structural highlights

3jps 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:	3jpn, 3jpo, 3jpp, 3jpq, 3jpr, 3jpt
Gene:	POLB (HUMAN)
Activity:	DNA-directed DNA polymerase, with EC number 2.7.7.7
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]

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

beta,gamma-Fluoromethylene analogues of nucleotides are considered to be useful mimics of the natural substrates, but direct structural evidence defining their active site interactions has not been available, including the influence of the new chiral center introduced at the CHF carbon, as in beta,gamma-fluoromethylene-dGTP, which forms an active site complex with DNA polymerase beta, a repair enzyme that plays an important role in base excision repair (BER) and oncogenesis. We report X-ray crystallographic results for a series of beta,gamma-CXY dGTP analogues, where X,Y = H, F, Cl, Br, and/or CH(3). For all three R/S monofluorinated analogues examined (CHF, 3/4; CCH(3)F, 13/14; CClF 15/16), a single CXF-diastereomer (3, 13, 16) is observed in the active site complex, with the CXF fluorine atom at a approximately 3 A (bonding) distance to a guanidinium N of Arg183. In contrast, for the CHCl, CHBr, and CHCH(3) analogues, both diasteromers (6/7, 8/9, 10/11) populate the dGTP site in the enzyme complex about equally. The structures of the bound dichloro (5) and dimethyl (12) analogue complexes indicate little to no steric effect on the placement of the bound nucleotide backbone. The results suggest that introduction of a single fluorine atom at the beta,gamma-bridging carbon atom of these dNTP analogues enables a new, stereospecific interaction within the preorganized active site complex that is unique to fluorine. The results also provide the first diverse structural data set permitting an assessment of how closely this class of dNTP analogues mimics the conformation of the parent nucleotide within the active site complex.

Halogenated beta,gamma-Methylene- and Ethylidene-dGTP-DNA Ternary Complexes with DNA Polymerase beta: Structural Evidence for Stereospecific Binding of the Fluoromethylene Analogues.,Batra VK, Pedersen LC, Beard WA, Wilson SH, Kashemirov BA, Upton TG, Goodman MF, McKenna CE J Am Chem Soc. 2010 May 13. PMID:20465217^[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, Pedersen LC, Beard WA, Wilson SH, Kashemirov BA, Upton TG, Goodman MF, McKenna CE. Halogenated beta,gamma-Methylene- and Ethylidene-dGTP-DNA Ternary Complexes with DNA Polymerase beta: Structural Evidence for Stereospecific Binding of the Fluoromethylene Analogues. J Am Chem Soc. 2010 May 13. PMID:20465217 doi:10.1021/ja909370k

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3jps"

@@ Line 1: / Line 1: @@
 ==Ternary complex of DNA polymerase beta with a dideoxy terminated primer and 2'-deoxyguanosine 5'-beta, gamma-fluoro methyl methylene triphosphate==
 <StructureSection load='3jps' size='340' side='right' caption='[[3jps]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3jps]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JPS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3jps]] 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=3JPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JPS 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=GFM:2-DEOXY-5-O-[(S)-{[(S)-[(1R)-1-FLUORO-1-PHOSPHONOETHYL](HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]GUANOSINE'>GFM</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=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jpn|3jpn]], [[3jpo|3jpo]], [[3jpp|3jpp]], [[3jpq|3jpq]], [[3jpr|3jpr]], [[3jpt|3jpt]]</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 Homo sapiens])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></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=3jps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jps OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3jps RCSB], [http://www.ebi.ac.uk/pdbsum/3jps PDBsum]</span></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=3jps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jps OCA], [http://pdbe.org/3jps PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jps RCSB], [http://www.ebi.ac.uk/pdbsum/3jps PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jps ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 21: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3jps ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 30: / Line 31: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3jps" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 38: / Line 40: @@
 </StructureSection>
 [[Category: DNA-directed DNA polymerase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Batra, V K]]
 [[Category: Beard, W A]]

3jps

From Proteopedia

Revision as of 08:35, 5 August 2016

Ternary complex of DNA polymerase beta with a dideoxy terminated primer and 2'-deoxyguanosine 5'-beta, gamma-fluoro methyl methylene triphosphate

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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