View source for 3mfh


==DNA Polymerase Eta in Complex With Undamaged DNA==
<StructureSection load='3mfh' size='340' side='right' caption='[[3mfh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3mfh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MFH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MFH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jih|1jih]], [[3mfi|3mfi]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAD30, DBH1, YDR419W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=3mfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mfh OCA], [http://pdbe.org/3mfh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mfh RCSB], [http://www.ebi.ac.uk/pdbsum/3mfh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mfh ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/POLH_YEAST POLH_YEAST]] 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. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. Efficiently incorporates nucleotides opposite to other UV or oxidative DNA damages like O(6)-methylguanine, 7,8-dihydro-8-oxoguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine of 2'-deoxyguanosine (FaPydG), or p-benzoquinone DNA adducts.<ref>PMID:9409821</ref> <ref>PMID:10347143</ref> <ref>PMID:10601233</ref> <ref>PMID:9974380</ref> <ref>PMID:10924462</ref> <ref>PMID:10713149</ref> <ref>PMID:11027270</ref> <ref>PMID:10932195</ref> <ref>PMID:10725365</ref> <ref>PMID:11062246</ref> <ref>PMID:11545742</ref> <ref>PMID:11113193</ref> <ref>PMID:11238937</ref> <ref>PMID:11054429</ref> <ref>PMID:12110599</ref> <ref>PMID:11861920</ref> <ref>PMID:12899630</ref> <ref>PMID:12665597</ref> <ref>PMID:12888515</ref> <ref>PMID:12692307</ref> <ref>PMID:14527996</ref> <ref>PMID:15157108</ref> <ref>PMID:15544332</ref> <ref>PMID:15284331</ref> <ref>PMID:15333698</ref> <ref>PMID:15024063</ref> <ref>PMID:15779911</ref> <ref>PMID:16181813</ref> <ref>PMID:15520252</ref> <ref>PMID:16366567</ref> <ref>PMID:15743815</ref> <ref>PMID:16866379</ref> <ref>PMID:16387871</ref> <ref>PMID:16415180</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/mf/3mfh_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=3mfh ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.

Structural basis for the suppression of skin cancers by DNA polymerase eta.,Silverstein TD, Johnson RE, Jain R, Prakash L, Prakash S, Aggarwal AK Nature. 2010 Jun 24;465(7301):1039-43. PMID:20577207<ref>PMID:20577207</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3mfh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Atcc 18824]]
[[Category: DNA-directed DNA polymerase]]
[[Category: Aggarwal, A K]]
[[Category: Jain, R]]
[[Category: Johnson, R E]]
[[Category: Prakash, L]]
[[Category: Prakash, S]]
[[Category: Silverstein, T D]]
[[Category: Cpd]]
[[Category: Dna binding]]
[[Category: Dna damage]]
[[Category: Dna polymerase eta]]
[[Category: Dna repair]]
[[Category: Dna replication]]
[[Category: Dna synthesis]]
[[Category: Dna-directed dna polymerase]]
[[Category: Magnesium]]
[[Category: Metal binding]]
[[Category: Mutator protein]]
[[Category: Nucleotidyltransferase]]
[[Category: Nucleus]]
[[Category: Protein-dna complex]]
[[Category: Thymidine dimer]]
[[Category: Transferase-dna complex]]
[[Category: Uv-damage]]