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2w7o

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{{Seed}}
 
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[[Image:2w7o.png|left|200px]]
 
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==Structure and Activity of Bypass Synthesis by Human DNA Polymerase Kappa Opposite the 7,8-Dihydro-8-oxodeoxyguanosine Adduct==
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The line below this paragraph, containing "STRUCTURE_2w7o", creates the "Structure Box" on the page.
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<StructureSection load='2w7o' size='340' side='right'caption='[[2w7o]], [[Resolution|resolution]] 3.16&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2w7o]] is a 6 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=2W7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W7O FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.16&#8491;</td></tr>
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<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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene></td></tr>
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{{STRUCTURE_2w7o| PDB=2w7o | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2w7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w7o OCA], [https://pdbe.org/2w7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w7o RCSB], [https://www.ebi.ac.uk/pdbsum/2w7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w7o ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/POLK_HUMAN POLK_HUMAN] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity.<ref>PMID:10620008</ref> <ref>PMID:11024016</ref> <ref>PMID:12145297</ref> <ref>PMID:12444249</ref> <ref>PMID:12952891</ref> <ref>PMID:14630940</ref> <ref>PMID:15533436</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w7/2w7o_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2w7o ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human polymerase kappa (hPol kappa) is one of four eukaryotic Y-class DNA polymerases and may be an important element in the cellular response to polycyclic aromatic hydrocarbons such as benzo[a]pyrene, which can lead to reactive oxygenated metabolite-mediated oxidative stress. Here, we present a detailed analysis of the activity and specificity of hPol kappa bypass opposite the major oxidative adduct 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG). Unlike its archaeal homolog Dpo4, hPol kappa bypasses this lesion in an error-prone fashion by inserting mainly dATP. Analysis of transient-state kinetics shows diminished "bursts" for dATP:8-oxoG and dCTP:8-oxoG incorporation, indicative of non-productive complex formation, but dATP:8-oxoG insertion events that do occur are 2-fold more efficient than dCTP:G insertion events. Crystal structures of ternary hPol kappa complexes with adducted template-primer DNA reveal non-productive (dGTP and dATP) alignments of incoming nucleotide and 8-oxoG. Structural limitations placed upon the hPol kappa by interactions between the N-clasp and finger domains combined with stabilization of the syn-oriented template 8-oxoG through the side chain of Met-135 both appear to contribute to error-prone bypass. Mutating Leu-508 in the little finger domain of hPol kappa to lysine modulates the insertion opposite 8-oxoG toward more accurate bypass, similar to previous findings with Dpo4. Our structural and activity data provide insight into important mechanistic aspects of error-prone bypass of 8-oxoG by hPol kappa compared with accurate and efficient bypass of the lesion by Dpo4 and polymerase eta.
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===STRUCTURE AND ACTIVITY OF BYPASS SYNTHESIS BY HUMAN DNA POLYMERASE KAPPA OPPOSITE THE 7,8-DIHYDRO-8-OXODEOXYGUANOSINE ADDUCT===
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Structural and functional elucidation of the mechanism promoting error-prone synthesis by human DNA polymerase kappa opposite the 7,8-dihydro-8-oxo-2'-deoxyguanosine adduct.,Irimia A, Eoff RL, Guengerich FP, Egli M J Biol Chem. 2009 Aug 14;284(33):22467-80. Epub 2009 Jun 19. PMID:19542228<ref>PMID:19542228</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2w7o" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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2W7O is a 6 chains structure of sequences 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=2W7O OCA].
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*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
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[[Category: DNA-directed DNA polymerase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Egli, M.]]
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[[Category: Large Structures]]
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[[Category: Irimia, A.]]
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[[Category: Egli M]]
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[[Category: 8-oxo-2p-deoxy-guanosine-5p-monophosphate]]
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[[Category: Irimia A]]
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[[Category: Dgtp]]
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[[Category: Dna damage]]
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[[Category: Dna repair]]
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[[Category: Dna-binding protein]]
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[[Category: Human dna polymerase kappa]]
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[[Category: Translesion dna polymerase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 1 20:20:24 2009''
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Current revision

Structure and Activity of Bypass Synthesis by Human DNA Polymerase Kappa Opposite the 7,8-Dihydro-8-oxodeoxyguanosine Adduct

PDB ID 2w7o

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