4zql: Difference between revisions

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'''Unreleased structure'''
==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=''>
The entry 4zql is ON HOLD
== Structural highlights ==
 
<table><tr><td colspan='2'>[[4zql]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZQL FirstGlance]. <br>
Authors: Tallant, C., Structural Genomics Consortium (SGC), Clark, P.G.K., Vieira, L.C.C., Krojer, T., Nunez-Alonso, G., Picaud, S., Fedorov, O., Dixon, D.J., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Brennan, P.E., Knapp, S.
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zql OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zql RCSB], [http://www.ebi.ac.uk/pdbsum/4zql PDBsum]</span></td></tr>
Description: 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
</table>
[[Category: Unreleased Structures]]
== Disease ==
[[Category: Nunez-Alonso, G]]
[[http://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN]] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:[http://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 ==
[[http://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: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Brennan, P E]]
[[Category: Clark, P G.K]]
[[Category: Delft, F von]]
[[Category: Dixon, D J]]
[[Category: Edwards, A M]]
[[Category: Fedorov, O]]
[[Category: Fedorov, O]]
[[Category: Vieira, L.C.C]]
[[Category: Picaud, S]]
[[Category: Knapp, S]]
[[Category: Knapp, S]]
[[Category: Krojer, T]]
[[Category: Krojer, T]]
[[Category: Structural Genomics Consortium (Sgc), Clark, P.G.K]]
[[Category: Nunez-Alonso, G]]
[[Category: Bountra, C]]
[[Category: Picaud, S]]
[[Category: Arrowsmith, C.H]]
[[Category: Structural genomic]]
[[Category: Von Delft, F]]
[[Category: Edwards, A.M]]
[[Category: Dixon, D.J]]
[[Category: Brennan, P.E]]
[[Category: Tallant, C]]
[[Category: Tallant, C]]
[[Category: Vieira, L C.C]]
[[Category: E3 protein-ubiquitin ligase activity]]
[[Category: Histone h3 modification]]
[[Category: Ligase]]
[[Category: Sgc]]
[[Category: Transcriptional coactivator]]

Revision as of 18:33, 17 June 2015

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 inhibitorCrystal 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

Structural highlights

4zql is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
Resources:FirstGlance, OCA, RCSB, PDBsum

Disease

[TIF1A_HUMAN] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM: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

[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).[1] [2] [3]

References

  1. ↑ Teyssier C, Ou CY, Khetchoumian K, Losson R, Stallcup MR. Transcriptional intermediary factor 1alpha mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor-interacting protein 1 nuclear receptor coactivators. Mol Endocrinol. 2006 Jun;20(6):1276-86. Epub 2005 Dec 1. PMID:16322096 doi:10.1210/me.2005-0393
  2. ↑ Allton K, Jain AK, Herz HM, Tsai WW, Jung SY, Qin J, Bergmann A, Johnson RL, Barton MC. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11612-6. doi:, 10.1073/pnas.0813177106. Epub 2009 Jun 25. PMID:19556538 doi:10.1073/pnas.0813177106
  3. ↑ Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, Tsai CY, Shi X, Schwarzer D, Plunkett W, Aronow B, Gozani O, Fischle W, Hung MC, Patel DJ, Barton MC. TRIM24 links a non-canonical histone signature to breast cancer. Nature. 2010 Dec 16;468(7326):927-32. PMID:21164480 doi:10.1038/nature09542

4zql, resolution 1.79Å

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