View source for 3gv8


==Human DNA polymerase iota in complex with T template DNA and incoming dGTP==
<StructureSection load='3gv8' size='340' side='right' caption='[[3gv8]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gv8]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GV8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gv5|3gv5]], [[3gv7|3gv7]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POLI, RAD30B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3gv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gv8 OCA], [http://pdbe.org/3gv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gv8 RCSB], [http://www.ebi.ac.uk/pdbsum/3gv8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gv8 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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/gv/3gv8_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=3gv8 ConSurf].
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== Publication Abstract from PubMed ==
Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP and dTTP maintain anti conformations with normal base stacking. Further stabilization of dGTP by H-bonding with Gln59 of the finger domain explains the preferential T to G mismatch. A template 'U-turn' is stabilized by pol and the methyl group of the thymine template, revealing the structural basis of T stalling. Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity.

Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase iota.,Kirouac KN, Ling H EMBO J. 2009 Jun 3;28(11):1644-54. PMID:19440206<ref>PMID:19440206</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 3gv8" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase|DNA polymerase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: DNA-directed DNA polymerase]]
[[Category: Human]]
[[Category: Kirouac, K N]]
[[Category: Ling, H]]
[[Category: Dna damage]]
[[Category: Dna repair]]
[[Category: Dna replication]]
[[Category: Dna synthesis]]
[[Category: Dna-binding]]
[[Category: Dna-directed dna polymerase]]
[[Category: Error prone replication]]
[[Category: Magnesium]]
[[Category: Metal-binding]]
[[Category: Mutator protein]]
[[Category: Nucleotidyltransferase]]
[[Category: Nucleus]]
[[Category: Polymerase iota]]
[[Category: Schiff base]]
[[Category: Transferase]]
[[Category: Transferase-dna complex]]
[[Category: Y-family polymerase]]