2ko0

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{{Seed}}
 
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[[Image:2ko0.png|left|200px]]
 
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==Solution structure of the THAP zinc finger of THAP1 in complex with its DNA target==
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The line below this paragraph, containing "STRUCTURE_2ko0", creates the "Structure Box" on the page.
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<StructureSection load='2ko0' size='340' side='right'caption='[[2ko0]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2ko0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KO0 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_2ko0| PDB=2ko0 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ko0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ko0 OCA], [https://pdbe.org/2ko0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ko0 RCSB], [https://www.ebi.ac.uk/pdbsum/2ko0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ko0 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/THAP1_HUMAN THAP1_HUMAN] Defects in THAP1 are the cause of dystonia type 6 (DYT6) [MIM:[https://omim.org/entry/602629 602629]. DYT6 is a primary torsion dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 6 is characterized by onset in early adulthood, cranial or cervical involvement in about half of the cases, and frequent progression to involve multiple body regions.[:]<ref>PMID:19345147</ref> <ref>PMID:19908325</ref> <ref>PMID:19908320</ref> <ref>PMID:19182804</ref> <ref>PMID:20629133</ref> <ref>PMID:20669277</ref> <ref>PMID:20687191</ref> <ref>PMID:20083799</ref> <ref>PMID:20211909</ref> <ref>PMID:21847143</ref> <ref>PMID:20825472</ref> <ref>PMID:21800139</ref> <ref>PMID:21839475</ref> <ref>PMID:21425335</ref> <ref>PMID:21425341</ref> <ref>PMID:21110056</ref> <ref>PMID:22377579</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/THAP1_HUMAN THAP1_HUMAN] DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. Specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes, including RRM1. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. May also have pro-apoptopic activity by potentiating both serum-withdrawal and TNF-induced apoptosis.<ref>PMID:12717420</ref> <ref>PMID:17003378</ref> <ref>PMID:20200153</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ko/2ko0_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2ko0 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human THAP1 is the prototype of a large family of cellular factors sharing an original THAP zinc-finger motif responsible for DNA binding. Human THAP1 regulates endothelial cell proliferation and G1/S cell-cycle progression, through modulation of pRb/E2F cell-cycle target genes including rrm1. Recently, mutations in THAP1 have been found to cause DYT6 primary torsion dystonia, a human neurological disease. We report here the first 3D structure of the complex formed by the DNA-binding domain of THAP1 and its specific DNA target (THABS) found within the rrm1 target gene. The THAP zinc finger uses its double-stranded beta-sheet to fill the DNA major groove and provides a unique combination of contacts from the beta-sheet, the N-terminal tail and surrounding loops toward the five invariant base pairs of the THABS sequence. Our studies reveal unprecedented insights into the specific DNA recognition mechanisms within this large family of proteins controlling cell proliferation, cell cycle and pluripotency.
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===Solution structure of the THAP zinc finger of THAP1 in complex with its DNA target===
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Structural determinants of specific DNA-recognition by the THAP zinc finger.,Campagne S, Saurel O, Gervais V, Milon A Nucleic Acids Res. 2010 Jun;38(10):3466-76. Epub 2010 Feb 9. PMID:20144952<ref>PMID:20144952</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_20144952}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2ko0" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 20144952 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20144952}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2KO0 is a 3 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KO0 OCA].
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==Reference==
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<ref group="xtra">PMID:20144952</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Campagne, S.]]
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[[Category: Large Structures]]
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[[Category: Gervais, V.]]
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[[Category: Campagne S]]
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[[Category: Milon, A.]]
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[[Category: Gervais V]]
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[[Category: Saurel, O.]]
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[[Category: Milon A]]
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[[Category: Ccch]]
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[[Category: Saurel O]]
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[[Category: Coiled coil]]
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[[Category: Dna binding domain]]
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[[Category: Dna-binding]]
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[[Category: Metal-binding]]
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[[Category: Nucleus]]
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[[Category: Protein-dna complex]]
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[[Category: Transcription factor]]
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[[Category: Transcription-dna complex]]
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[[Category: Zinc finger]]
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[[Category: Zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 21 08:31:19 2010''
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Current revision

Solution structure of the THAP zinc finger of THAP1 in complex with its DNA target

PDB ID 2ko0

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