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[[Image:2dpi.gif|left|200px]]
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{{STRUCTURE_2dpi|  PDB=2dpi  |  SCENE=  }}
'''Ternary complex of hPoli with DNA and dCTP'''


==Ternary complex of hPoli with DNA and dCTP==
<StructureSection load='2dpi' size='340' side='right'caption='[[2dpi]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2dpi]] is a 3 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=2DPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DPI 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=EDA:3-[2-DEOXY-RIBOFURANOSYL]-3H-1,3,4,5A,8-PENTAAZA-AS-INDACENE-5-MONOPHOSPHATE'>EDA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2dpi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dpi OCA], [https://pdbe.org/2dpi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dpi RCSB], [https://www.ebi.ac.uk/pdbsum/2dpi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dpi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLI_HUMAN POLI_HUMAN] Error-prone 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. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.<ref>PMID:11013228</ref> <ref>PMID:11251121</ref> <ref>PMID:11387224</ref> <ref>PMID:12410315</ref> <ref>PMID:14630940</ref> <ref>PMID:15199127</ref> <ref>PMID:15254543</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/dp/2dpi_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=2dpi ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The 1,N6-ethenodeoxyadenosine (epsilon dA) lesion is promutagenic and has been implicated in carcinogenesis. We show here that human Pol iota, a Y-family DNA polymerase, can promote replication through this lesion by proficiently incorporating a nucleotide opposite it. The structural basis of this action is rotation of the epsilon dA adduct to the syn conformation in the Pol iota active site and presentation of its 'Hoogsteen edge' for hydrogen-bonding with incoming dTTP or dCTP. We also show that Pol zeta carries out the subsequent extension reaction and that efficiency of extension from epsilon dA x T is notably higher than from epsilon dA x C. Together, our studies reveal for the first time how the exocyclic epsilon dA adduct is accommodated in a DNA polymerase active site, and they show that the combined action of Pol iota and Pol zeta provides for efficient and error-free synthesis through this potentially carcinogenic DNA lesion.


==Overview==
Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota.,Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK Nat Struct Mol Biol. 2006 Jul;13(7):619-25. Epub 2006 Jul 2. PMID:16819516<ref>PMID:16819516</ref>
The 1,N6-ethenodeoxyadenosine (epsilon dA) lesion is promutagenic and has been implicated in carcinogenesis. We show here that human Pol iota, a Y-family DNA polymerase, can promote replication through this lesion by proficiently incorporating a nucleotide opposite it. The structural basis of this action is rotation of the epsilon dA adduct to the syn conformation in the Pol iota active site and presentation of its 'Hoogsteen edge' for hydrogen-bonding with incoming dTTP or dCTP. We also show that Pol zeta carries out the subsequent extension reaction and that efficiency of extension from epsilon dA x T is notably higher than from epsilon dA x C. Together, our studies reveal for the first time how the exocyclic epsilon dA adduct is accommodated in a DNA polymerase active site, and they show that the combined action of Pol iota and Pol zeta provides for efficient and error-free synthesis through this potentially carcinogenic DNA lesion.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2DPI is a [[Single protein]] structure of sequence 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=2DPI OCA].
</div>
<div class="pdbe-citations 2dpi" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota., Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK, Nat Struct Mol Biol. 2006 Jul;13(7):619-25. Epub 2006 Jul 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16819516 16819516]
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
[[Category: DNA-directed DNA polymerase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Aggarwal, A K.]]
[[Category: Aggarwal AK]]
[[Category: Johnson, R E.]]
[[Category: Johnson RE]]
[[Category: Nair, D T.]]
[[Category: Nair DT]]
[[Category: Prakash, L.]]
[[Category: Prakash L]]
[[Category: Prakash, S.]]
[[Category: Prakash S]]
[[Category: Dna dependent dna polymerase]]
[[Category: Ethenoda adduct]]
[[Category: Lesion bypass]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 00:54:53 2008''

Latest revision as of 08:28, 25 October 2023

Ternary complex of hPoli with DNA and dCTP

2dpi, resolution 2.30Å

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