5i29
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==TAF1(2) bound to a pyrrolopyridone compound== | |
| + | <StructureSection load='5i29' size='340' side='right' caption='[[5i29]], [[Resolution|resolution]] 1.21Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5i29]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I29 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I29 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=67B:N,N-DIMETHYL-3-(6-METHYL-7-OXO-6,7-DIHYDRO-1H-PYRROLO[2,3-C]PYRIDIN-4-YL)BENZAMIDE'>67B</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5i1q|5i1q]]</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=5i29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i29 OCA], [http://pdbe.org/5i29 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i29 RCSB], [http://www.ebi.ac.uk/pdbsum/5i29 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/TAF1_HUMAN TAF1_HUMAN]] Defects in TAF1 are the cause of dystonia type 3 (DYT3) [MIM:[http://omim.org/entry/314250 314250]]; also called X-linked dystonia-parkinsonism (XDP). DYT3 is a X-linked dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT3 is characterized by severe progressive torsion dystonia followed by parkinsonism. Its prevalence is high in the Philippines. DYT3 has a well-defined pathology of extensive neuronal loss and mosaic gliosis in the striatum (caudate nucleus and putamen) which appears to resemble that in Huntington disease.<ref>PMID:12928496</ref> <ref>PMID:17273961</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/TAF1_HUMAN TAF1_HUMAN]] Largest component and core scaffold of the TFIID basal transcription factor complex. Contains novel N- and C-terminal Ser/Thr kinase domains which can autophosphorylate or transphosphorylate other transcription factors. Phosphorylates TP53 on 'Thr-55' which leads to MDM2-mediated degradation of TP53. Phosphorylates GTF2A1 and GTF2F1 on Ser residues. Possesses DNA-binding activity. Essential for progression of the G1 phase of the cell cycle.<ref>PMID:2038334</ref> <ref>PMID:8450888</ref> <ref>PMID:8625415</ref> <ref>PMID:9660973</ref> <ref>PMID:9858607</ref> <ref>PMID:11278496</ref> <ref>PMID:15053879</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The biological role played by non-BET bromodomains remains poorly understood, and it is therefore imperative to identify potent and highly selective inhibitors to effectively explore the biology of individual bromodomain proteins. A ligand-efficient nonselective bromodomain inhibitor was identified from a 6-methyl pyrrolopyridone fragment. Small hydrophobic substituents replacing the N-methyl group were designed directing toward the conserved bromodomain water pocket, and two distinct binding conformations were then observed. The substituents either directly displaced and rearranged the conserved solvent network, as in BRD4(1) and TAF1(2), or induced a narrow hydrophobic channel adjacent to the lipophilic shelf, as in BRD9 and CECR2. The preference of distinct substituents for individual bromodomains provided selectivity handles useful for future lead optimization efforts for selective BRD9, CECR2, and TAF1(2) inhibitors. | ||
| - | + | Diving into the Water: Inducible Binding Conformations for BRD4, TAF1(2), BRD9, and CECR2 Bromodomains.,Crawford TD, Tsui V, Flynn EM, Wang S, Taylor AM, Cote A, Audia JE, Beresini MH, Burdick DJ, Cummings R, Dakin LA, Duplessis M, Good AC, Hewitt MC, Huang HR, Jayaram H, Kiefer JR, Jiang Y, Murray J, Nasveschuk CG, Pardo E, Poy F, Romero FA, Tang Y, Wang J, Xu Z, Zawadzke LE, Zhu X, Albrecht BK, Magnuson SR, Bellon S, Cochran AG J Med Chem. 2016 Jun 9;59(11):5391-402. doi: 10.1021/acs.jmedchem.6b00264. Epub, 2016 May 31. PMID:27219867<ref>PMID:27219867</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5i29" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bellon, S F]] | ||
| + | [[Category: Poy, F]] | ||
| + | [[Category: Tang, Y]] | ||
| + | [[Category: Inhibitor-bound]] | ||
| + | [[Category: Protein binding-inhibitor complex]] | ||
| + | [[Category: Second bromodomain of taf1]] | ||
Revision as of 15:26, 20 June 2016
TAF1(2) bound to a pyrrolopyridone compound
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