View source for 2v4q


==Post-insertion complex of the Y-family DNA polymerase Dpo4 with M1dG containing template DNA==
<StructureSection load='2v4q' size='340' side='right'caption='[[2v4q]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2v4q]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Sulso Sulso]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V4Q OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2V4Q FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M1G:3-(2-DEOXY-BETA-D-RIBOFURANOSYL)-PYRIDO[5,6-A]-PURINE-10-ONE-5-MONOPHOSPHATE'>M1G</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1s0m|1s0m]], [[2asl|2asl]], [[2jeg|2jeg]], [[1rys|1rys]], [[2j6t|2j6t]], [[1n56|1n56]], [[2atl|2atl]], [[1jx4|1jx4]], [[2c22|2c22]], [[2va2|2va2]], [[1s97|1s97]], [[2agq|2agq]], [[2jej|2jej]], [[2ago|2ago]], [[2asj|2asj]], [[2asd|2asd]], [[1n48|1n48]], [[1jxl|1jxl]], [[2bq3|2bq3]], [[2j6u|2j6u]], [[2uvu|2uvu]], [[2agp|2agp]], [[2c2r|2c2r]], [[1s0n|1s0n]], [[1s0o|1s0o]], [[2jef|2jef]], [[2uvw|2uvw]], [[2bqr|2bqr]], [[2jei|2jei]], [[2bqu|2bqu]], [[2au0|2au0]], [[1s9f|1s9f]], [[2c28|2c28]], [[2v9w|2v9w]], [[2c2e|2c2e]], [[1ryr|1ryr]], [[2c2d|2c2d]], [[2uvv|2uvv]], [[1s10|1s10]], [[2j6s|2j6s]], [[2br0|2br0]], [[2uvr|2uvr]], [[2va3|2va3]], [[2v4r|2v4r]], [[2v4s|2v4s]], [[2v4t|2v4t]]</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://proteopedia.org/fgij/fg.htm?mol=2v4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4q OCA], [http://pdbe.org/2v4q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2v4q RCSB], [http://www.ebi.ac.uk/pdbsum/2v4q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2v4q ProSAT]</span></td></tr>
</table>
== 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/v4/2v4q_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=2v4q ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Oxidative stress can induce the formation of reactive electrophiles, such as DNA peroxidation products, e.g. base propenals, and lipid peroxidation products, e.g. malondialdehyde. Base propenals and malondialdehyde react with DNA to form adducts, including 3-(2'-deoxy-ss-D-erythro-pentofuranosyl)-pyrimido[1,2-alpha]purin-10(3H)-o ne (M1dG). When paired opposite cytosine in duplex DNA at physiological pH, M1dG undergoes ring opening to form N2-(3-oxo-1-propenyl)-dG (N2-OPdG). Previous work has shown that M1dG is mutagenic in bacteria and mammalian cells and that its mutagenicity in Escherichia coli is dependent on induction of the SOS response, indicating a role for translesion DNA polymerases in the bypass of M1dG. To probe the mechanism by which translesion polymerases bypass M1dG, kinetic and structural studies were conducted with a model Y-family DNA polymerase, Dpo4 from Sulfolobus solfataricus. Steady-state incorporation of dNTPs opposite M1dG was reduced 260- to 2,900-fold and exhibited a preference for dATP incorporation. LC-MS/MS analysis of the full-length extension products revealed a spectrum of products arising principally by incorporation of dC or dA opposite M1dG followed by partial or full-length extension. A greater proportion of -1 deletions were observed when dT was positioned 5' of M1dG. Two crystal structures were solved, including a "Type II" frameshift deletion complex and another complex with Dpo4 bound to a dC:M1dG pair located in the post-insertion context. Importantly, M1dG was in the ring-closed state in both structures and in the structure with dC opposite M1dG, the dC residue moved out of the Dpo4 active site, into the minor groove. The results are consistent with the reported mutagenicity of M1dG and illustrate how the lesion may affect replication events.

Structural and Functional Analysis of Sulfolobus solfataricus Y-family DNA polymerase Dpo4-catalyzed Bypass of the Malondialdehyde-deoxyguanosine Adduct.,Eoff RL, Stafford JB, Szekely J, Rizzo CJ, Egli M, Guengerich FP, Marnett LJ Biochemistry. 2009 Jun 4. PMID:19492857<ref>PMID:19492857</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2v4q" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: DNA-directed DNA polymerase]]
[[Category: Large Structures]]
[[Category: Sulso]]
[[Category: Egli, M]]
[[Category: Eoff, R L]]
[[Category: Guengerich, F P]]
[[Category: Marnett, L J]]
[[Category: Rizzo, C J]]
[[Category: Stafford, J B]]
[[Category: Szekely, J]]
[[Category: Cytoplasm]]
[[Category: Dna adduct]]
[[Category: Dna damage]]
[[Category: Dna repair]]
[[Category: Dna replication]]
[[Category: Dna-binding]]
[[Category: Dna-directed dna polymerase]]
[[Category: Dpo4]]
[[Category: M1dg]]
[[Category: Magnesium]]
[[Category: Metal-binding]]
[[Category: Mutator protein]]
[[Category: Nucleotidyltransferase]]
[[Category: Polymerase]]
[[Category: Transferase]]