View source for 2w9c


==Ternary complex of Dpo4 bound to N2,N2-dimethyl-deoxyguanosine modified DNA with incoming dTTP==
<StructureSection load='2w9c' size='340' side='right'caption='[[2w9c]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2w9c]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus_P2 Saccharolobus solfataricus P2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2W9C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W9C 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=O2G:2-DEOXY-N,N-DIMETHYL-5-O-[OXIDO(OXO)PHOSPHONIO]GUANOSINE'>O2G</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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=2w9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w9c OCA], [https://pdbe.org/2w9c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w9c RCSB], [https://www.ebi.ac.uk/pdbsum/2w9c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w9c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPO4_SACS2 DPO4_SACS2] Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis.
== 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/w9/2w9c_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=2w9c ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Previous work has shown that Y-family DNA polymerases tolerate large DNA adducts, but a substantial decrease in catalytic efficiency and fidelity occurs during bypass of N(2),N(2)-dimethyl (Me(2))-substituted guanine (N(2),N(2)-Me(2)G), in contrast to a single methyl substitution. Therefore, it is unclear why the addition of two methyl groups is so disruptive. The presence of N(2),N(2)-Me(2)G lowered the catalytic efficiency of the model enzyme Sulfolobus solfataricus Dpo4 16,000-fold. Dpo4 inserted dNTPs almost at random during bypass of N(2),N(2)-Me(2)G, and much of the enzyme was kinetically trapped by an inactive ternary complex when N(2),N(2)-Me(2)G was present, as judged by a reduced burst amplitude (5% of total enzyme) and kinetic modeling. One crystal structure of Dpo4 with a primer having a 3'-terminal dideoxycytosine (C(dd)) opposite template N(2),N(2)-Me(2)G in a post-insertion position showed C(dd) folded back into the minor groove, as a catalytically incompetent complex. A second crystal had two unique orientations for the primer terminal C(dd) as follows: (i) flipped into the minor groove and (ii) a long pairing with N(2),N(2)-Me(2)G in which one hydrogen bond exists between the O-2 atom of C(dd) and the N-1 atom of N(2),N(2)-Me(2)G, with a second water-mediated hydrogen bond between the N-3 atom of C(dd) and the O-6 atom of N(2),N(2)-Me(2)G. A crystal structure of Dpo4 with dTTP opposite template N(2),N(2)-Me(2)G revealed a wobble orientation. Collectively, these results explain, in a detailed manner, the basis for the reduced efficiency and fidelity of Dpo4-catalyzed bypass of N(2),N(2)-Me(2)G compared with mono-substituted N(2)-alkyl G adducts.

Structure-Function Relationships in Miscoding by Sulfolobus solfataricus DNA Polymerase Dpo4: GUANINE N2,N2-DIMETHYL SUBSTITUTION PRODUCES INACTIVE AND MISCODING POLYMERASE COMPLEXES.,Zhang H, Eoff RL, Kozekov ID, Rizzo CJ, Egli M, Guengerich FP J Biol Chem. 2009 Jun 26;284(26):17687-99. PMID:19542237<ref>PMID:19542237</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2w9c" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharolobus solfataricus P2]]
[[Category: Egli M]]
[[Category: Eoff RL]]
[[Category: Guengerich FP]]
[[Category: Kosekov ID]]
[[Category: Rizzo CJ]]
[[Category: Zhang H]]