View source for 4zql


==Crystal structure of TRIM24 with 3,4-dimethoxy-N-(6-(4-methoxyphenoxy)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)benzenesulfonamide inhibitor==
<StructureSection load='4zql' size='340' side='right'caption='[[4zql]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zql]] is a 2 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=4ZQL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZQL 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]] 1.79&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=4QH:3,4-DIMETHOXY-N-[6-(4-METHOXYPHENOXY)-1,3-DIMETHYL-2-OXO-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL]BENZENESULFONAMIDE'>4QH</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4zql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zql OCA], [https://pdbe.org/4zql PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zql RCSB], [https://www.ebi.ac.uk/pdbsum/4zql PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zql ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:[https://omim.org/entry/188550 188550]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.
== Function ==
[https://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN] Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).<ref>PMID:16322096</ref> <ref>PMID:19556538</ref> <ref>PMID:21164480</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Brennan PE]]
[[Category: Clark PGK]]
[[Category: Dixon DJ]]
[[Category: Edwards AM]]
[[Category: Fedorov O]]
[[Category: Knapp S]]
[[Category: Krojer T]]
[[Category: Nunez-Alonso G]]
[[Category: Picaud S]]
[[Category: Tallant C]]
[[Category: Vieira LCC]]
[[Category: Von Delft F]]