7k6f: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(One intermediate revision by the same user not shown)
Line 3: Line 3:
<StructureSection load='7k6f' size='340' side='right'caption='[[7k6f]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
<StructureSection load='7k6f' size='340' side='right'caption='[[7k6f]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7k6f]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K6F FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K6F FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=7k6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k6f OCA], [https://pdbe.org/7k6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k6f RCSB], [https://www.ebi.ac.uk/pdbsum/7k6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k6f ProSAT]</span></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=7k6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k6f OCA], [https://pdbe.org/7k6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k6f RCSB], [https://www.ebi.ac.uk/pdbsum/7k6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k6f ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/TAF1_HUMAN TAF1_HUMAN]] Defects in TAF1 are the cause of dystonia type 3 (DYT3) [MIM:[https://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 ==
[[https://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 ==
Bromodomains regulate chromatin remodeling and gene transcription through recognition of acetylated lysines on histones and other proteins. Bromodomain-containing protein TAF1, a subunit of general transcription factor TFIID, initiates preinitiation complex formation and cellular transcription. TAF1 serves as a cofactor for certain oncogenic transcription factors and is implicated in regulating the p53 tumor suppressor. Therefore, TAF1 is a potential target to develop small molecule therapeutics for diseases arising from dysregulated transcription, such as cancer. Here, we report the ATR kinase inhibitor AZD6738 (Ceralasertib) and analogues thereof as bona fide inhibitors of TAF1. Crystallographic and small-angle X-ray scattering studies established that newly identified and previously reported inhibitors stabilize distinct structural states of the TAF1 tandem bromodomain through "open-closed" transitions and dimerization. Combined with functional studies on p53 signaling in cancer cell lines, the data provide new insights into the feasibility and challenges of TAF1 inhibitors as chemical probes and therapeutics.


Discovery of Dual TAF1-ATR Inhibitors and Ligand-Induced Structural Changes of the TAF1 Tandem Bromodomain.,Karim RM, Yang L, Chen L, Bikowitz MJ, Lu J, Grassie D, Shultz ZP, Lopchuk JM, Chen J, Schonbrunn E J Med Chem. 2022 Feb 22. doi: 10.1021/acs.jmedchem.1c01999. PMID:35191694<ref>PMID:35191694</ref>
==See Also==
 
*[[Transcription initiation factors 3D structures|Transcription initiation factors 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7k6f" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bikowitz, M J]]
[[Category: Bikowitz MJ]]
[[Category: Karim, M R]]
[[Category: Karim MR]]
[[Category: Schonbrunn, E]]
[[Category: Schonbrunn E]]
[[Category: Atr]]
[[Category: Bet]]
[[Category: Dual brd-kinase]]
[[Category: Gene regulation]]
[[Category: Kinase inhibitor]]
[[Category: Non-bet]]
[[Category: Taf1]]
[[Category: Transferase]]

Latest revision as of 14:04, 23 October 2024

Crystal structure of the tandem bromodomain (BD1, BD2) of human TAF1 in complex with MES (2-(N-morpholino)ethanesulfonic acid)Crystal structure of the tandem bromodomain (BD1, BD2) of human TAF1 in complex with MES (2-(N-morpholino)ethanesulfonic acid)

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.86Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

See Also

7k6f, resolution 1.86Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=7k6f&oldid=4232472"