1mq3: Difference between revisions

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New page: left|200px<br /> <applet load="1mq3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mq3, resolution 2.8Å" /> '''Human DNA Polymerase...
 
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[[Image:1mq3.gif|left|200px]]<br />
<applet load="1mq3" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1mq3, resolution 2.8&Aring;" />
'''Human DNA Polymerase Beta Complexed With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine Template Paired with dCTP'''<br />


==Overview==
==Human DNA Polymerase Beta Complexed With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine Template Paired with dCTP==
Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine, (8-oxodG). During DNA replication and repair synthesis, 8-oxodG can pair, with cytosine or adenine. The ability to accurately replicate through this, lesion depends on the DNA polymerase. We report the first structure of a, polymerase with a promutagenic DNA lesion, 8-oxodG, in the confines of its, active site. The modified guanine residue is in an anti conformation and, forms Watson-Crick hydrogen bonds with an incoming dCTP. To accommodate, the oxygen at C8, the 5'-phosphate backbone of the templating nucleotide, flips 180 degrees. Thus, the flexibility of the template sugar-phosphate, backbone near the polymerase active site is one parameter that influences, the anti-syn equilibrium of 8-oxodG. Our results provide insights into the, mechanisms employed by polymerases to select the complementary dNTP.
<StructureSection load='1mq3' size='340' side='right'caption='[[1mq3]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1mq3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MQ3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=1mq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mq3 OCA], [https://pdbe.org/1mq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mq3 RCSB], [https://www.ebi.ac.uk/pdbsum/1mq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mq3 ProSAT]</span></td></tr>
</table>
== 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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mq/1mq3_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <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/main_output.php?pdb_ID=1mq3 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1MQ3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, NA and DCP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MQ3 OCA].
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 
== References ==
==Reference==
<references/>
Structure of DNA polymerase beta with the mutagenic DNA lesion 8-oxodeoxyguanine reveals structural insights into its coding potential., Krahn JM, Beard WA, Miller H, Grollman AP, Wilson SH, Structure. 2003 Jan;11(1):121-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12517346 12517346]
__TOC__
[[Category: DNA-directed DNA polymerase]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Beard, W.A.]]
[[Category: Beard WA]]
[[Category: Grollman, A.P.]]
[[Category: Grollman AP]]
[[Category: Krahn, J.M.]]
[[Category: Krahn JM]]
[[Category: Miller, H.]]
[[Category: Miller H]]
[[Category: Wilson, S.H.]]
[[Category: Wilson SH]]
[[Category: DCP]]
[[Category: MG]]
[[Category: NA]]
[[Category: dna]]
[[Category: transferase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:13:53 2007''

Latest revision as of 10:47, 14 February 2024

Human DNA Polymerase Beta Complexed With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine Template Paired with dCTPHuman DNA Polymerase Beta Complexed With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine Template Paired with dCTP

Structural highlights

1mq3 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:, , , ,
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.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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

1mq3, resolution 2.80Å

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