1tk0: Difference between revisions

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[[Image:1tk0.png|left|200px]]
==T7 DNA polymerase ternary complex with 8 oxo guanosine and ddCTP at the insertion site==
<StructureSection load='1tk0' size='340' side='right' caption='[[1tk0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tk0]] is a 4 chain structure with sequence 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=1TK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TK0 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=DCT:2,3-DIDEOXYCYTIDINE+5-TRIPHOSPHATE'>DCT</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><br>
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1t8e|1t8e]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10760 Enterobacteria phage T7]), TRXA, TSNC, FIPA, B3781, C4701, Z5291, ECS4714, STM3915, STMD1.75, STY3639, T3381, SF3854, S3905 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tk0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1tk0 RCSB], [http://www.ebi.ac.uk/pdbsum/1tk0 PDBsum]</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/tk/1tk0_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/chain_selection.php?pdb_ID=2ata 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.


{{STRUCTURE_1tk0|  PDB=1tk0  |  SCENE=  }}
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>


===T7 DNA polymerase ternary complex with 8 oxo guanosine and ddCTP at the insertion site===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_15297882}}
 
==About this Structure==
[[1tk0]] is a 4 chain structure with sequence 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=1TK0 OCA].


==See Also==
==See Also==
*[[DNA polymerase|DNA polymerase]]
*[[DNA polymerase|DNA polymerase]]
*[[Thioredoxin|Thioredoxin]]
*[[Thioredoxin|Thioredoxin]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:015297882</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: DNA-directed DNA polymerase]]
[[Category: DNA-directed DNA polymerase]]
[[Category: Enterobacteria phage t7]]
[[Category: Enterobacteria phage t7]]

Revision as of 02:24, 29 September 2014

T7 DNA polymerase ternary complex with 8 oxo guanosine and ddCTP at the insertion siteT7 DNA polymerase ternary complex with 8 oxo guanosine and ddCTP at the insertion site

Structural highlights

1tk0 is a 4 chain structure with sequence from Enterobacteria phage t7 and Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
NonStd Res:,
Related:1t8e
Gene:5 (Enterobacteria phage T7), TRXA, TSNC, FIPA, B3781, C4701, Z5291, ECS4714, STM3915, STMD1.75, STY3639, T3381, SF3854, S3905 (Escherichia coli)
Activity:DNA-directed DNA polymerase, with EC number 2.7.7.7
Resources:FirstGlance, OCA, RCSB, PDBsum

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Brieba LG, Eichman BF, Kokoska RJ, Doublie S, Kunkel TA, Ellenberger T. Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase. EMBO J. 2004 Sep 1;23(17):3452-61. Epub 2004 Aug 5. PMID:15297882 doi:10.1038/sj.emboj.7600354

1tk0, resolution 2.30Å

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