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[[Image:1tkd.gif|left|200px]]
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{{STRUCTURE_1tkd|  PDB=1tkd  |  SCENE=  }}
'''T7 DNA polymerase ternary complex with 8 oxo guanosine and dCMP at the elongation site'''


==T7 DNA polymerase ternary complex with 8 oxo guanosine and dCMP at the elongation site==
<StructureSection load='1tkd' size='340' side='right'caption='[[1tkd]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tkd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Escherichia_phage_T7 Escherichia phage T7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TKD 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]] 2.49&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=D3T:2,3-DIDEOXY-THYMIDINE-5-TRIPHOSPHATE'>D3T</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tkd OCA], [https://pdbe.org/1tkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tkd RCSB], [https://www.ebi.ac.uk/pdbsum/1tkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tkd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPOL_BPT7 DPOL_BPT7] Replicates viral genomic DNA. Non-processive DNA polymerase that achieves processivity by binding to host thioredoxin (TrxA). This interaction increases the rate of dNTP incorporation to yield a processivity of approximately 800 nucleotides (nt) per binding event. Interacts with DNA helicase gp4 to coordinate nucleotide polymerization with unwinding of the DNA. The leading strand is synthesized continuously while synthesis of the lagging strand requires the synthesis of oligoribonucleotides by the primase domain of gp4.<ref>PMID:9218486</ref> <ref>PMID:21606333</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/tk/1tkd_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=1tkd ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Accurate DNA replication involves polymerases with high nucleotide selectivity and proofreading activity. We show here why both fidelity mechanisms fail when normally accurate T7 DNA polymerase bypasses the common oxidative lesion 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8oG). The crystal structure of the polymerase with 8oG templating dC insertion shows that the O8 oxygen is tolerated by strong kinking of the DNA template. A model of a corresponding structure with dATP predicts steric and electrostatic clashes that would reduce but not eliminate insertion of dA. The structure of a postinsertional complex shows 8oG(syn).dA (anti) in a Hoogsteen-like base pair at the 3' terminus, and polymerase interactions with the minor groove surface of the mismatch that mimic those with undamaged, matched base pairs. This explains why translesion synthesis is permitted without proofreading of an 8oG.dA mismatch, thus providing insight into the high mutagenic potential of 8oG.


==Overview==
Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase.,Brieba LG, Eichman BF, Kokoska RJ, Doublie S, Kunkel TA, Ellenberger T EMBO J. 2004 Sep 1;23(17):3452-61. Epub 2004 Aug 5. PMID:15297882<ref>PMID:15297882</ref>
Accurate DNA replication involves polymerases with high nucleotide selectivity and proofreading activity. We show here why both fidelity mechanisms fail when normally accurate T7 DNA polymerase bypasses the common oxidative lesion 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8oG). The crystal structure of the polymerase with 8oG templating dC insertion shows that the O8 oxygen is tolerated by strong kinking of the DNA template. A model of a corresponding structure with dATP predicts steric and electrostatic clashes that would reduce but not eliminate insertion of dA. The structure of a postinsertional complex shows 8oG(syn).dA (anti) in a Hoogsteen-like base pair at the 3' terminus, and polymerase interactions with the minor groove surface of the mismatch that mimic those with undamaged, matched base pairs. This explains why translesion synthesis is permitted without proofreading of an 8oG.dA mismatch, thus providing insight into the high mutagenic potential of 8oG.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1TKD is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Enterobacteria_phage_t7 Enterobacteria phage t7] and [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TKD OCA].
</div>
<div class="pdbe-citations 1tkd" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase., Brieba LG, Eichman BF, Kokoska RJ, Doublie S, Kunkel TA, Ellenberger T, EMBO J. 2004 Sep 1;23(17):3452-61. Epub 2004 Aug 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15297882 15297882]
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
[[Category: DNA-directed DNA polymerase]]
*[[Thioredoxin 3D structures|Thioredoxin 3D structures]]
[[Category: Enterobacteria phage t7]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Protein complex]]
[[Category: Escherichia phage T7]]
[[Category: Brieba, L G.]]
[[Category: Large Structures]]
[[Category: Doublie, S.]]
[[Category: Brieba LG]]
[[Category: Eichman, B F.]]
[[Category: Doublie S]]
[[Category: Ellenberger, T.]]
[[Category: Eichman BF]]
[[Category: Kokoska, R J.]]
[[Category: Ellenberger T]]
[[Category: Kunkel, T A.]]
[[Category: Kokoska RJ]]
[[Category: 8-oxoguanosine dna polymerase]]
[[Category: Kunkel TA]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 10:03:25 2008''

Latest revision as of 06:31, 23 August 2023

T7 DNA polymerase ternary complex with 8 oxo guanosine and dCMP at the elongation site

1tkd, resolution 2.49Å

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