7k03 - Revision history

OCA at 15:15, 18 October 2023

OCA — Wed, 18 Oct 2023 15:15:23 GMT

←Older revision		Revision as of 15:15, 18 October 2023
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	<StructureSection load='7k03' size='340' side='right'caption='[[7k03]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='7k03' size='340' side='right'caption='[[7k03]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7k03]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K03 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7k03]] is a 1 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=7K03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K03 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VJM:4-(4-{1-[(R)-amino(hydroxy)methyl-lambda~4~-sulfanyl]cyclopropyl}-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-2-yl)-1H-pyrrolo[2,3-b]pyridine'>VJM</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]] 1.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VJM:4-(4-{1-[(R)-amino(hydroxy)methyl-lambda~4~-sulfanyl]cyclopropyl}-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-2-yl)-1H-pyrrolo[2,3-b]pyridine'>VJM</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=7k03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k03 OCA], [https://pdbe.org/7k03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k03 RCSB], [https://www.ebi.ac.uk/pdbsum/7k03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k03 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=7k03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k03 OCA], [https://pdbe.org/7k03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k03 RCSB], [https://www.ebi.ac.uk/pdbsum/7k03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k03 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[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 ==		== 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>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7k03" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7k03" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Transcription initiation factors 3D structures\|Transcription initiation factors 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[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~~]]	+

OCA at 07:19, 9 March 2022

OCA — Wed, 09 Mar 2022 07:19:06 GMT

←Older revision		Revision as of 07:19, 9 March 2022
Line 1:		Line 1:

	==Crystal structure of the tandem bromodomain (BD1 and BD2) of human TAF1 bound to ATR kinase inhibitor AZD6738==		==Crystal structure of the tandem bromodomain (BD1 and BD2) of human TAF1 bound to ATR kinase inhibitor AZD6738==
-	<StructureSection load='7k03' size='340' side='right'caption='[[7k03]]' scene=''>	+	<StructureSection load='7k03' size='340' side='right'caption='[[7k03]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K03 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7k03]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K03 FirstGlance]. <br>
-	</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=7k03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k03 OCA], [https://pdbe.org/7k03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k03 RCSB], [https://www.ebi.ac.uk/pdbsum/7k03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k03 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VJM:4-(4-{1-[(R)-amino(hydroxy)methyl-lambda~4~-sulfanyl]cyclopropyl}-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-2-yl)-1H-pyrrolo[2,3-b]pyridine'>VJM</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=7k03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k03 OCA], [https://pdbe.org/7k03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k03 RCSB], [https://www.ebi.ac.uk/pdbsum/7k03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k03 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>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7k03" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Karim MR]]	+	[[Category: Karim, M R]]
-	[[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]]

OCA at 06:50, 22 September 2021

OCA — Wed, 22 Sep 2021 06:50:09 GMT

←Older revision		Revision as of 06:50, 22 September 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7k03 is ON HOLD until Sep 03 2022~~	+	==Crystal structure of the tandem bromodomain (BD1 and BD2) of human TAF1 bound to ATR kinase inhibitor AZD6738==
-		+	<StructureSection load='7k03' size='340' side='right'caption='[[7k03]]' scene=''>
-	~~Authors: Karim, M.R., Schonbrunn, E.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K03 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of the tandem bromodomain (BD1 and BD2) of human TAF1 bound to ATR kinase inhibitor AZD6738	+	</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=7k03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k03 OCA], [https://pdbe.org/7k03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k03 RCSB], [https://www.ebi.ac.uk/pdbsum/7k03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k03 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Karim~~, M.R~~]]	+	__TOC__
-	[[Category: Schonbrunn, E]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Karim MR]]
		+	[[Category: Schonbrunn E]]

OCA at 07:02, 16 September 2020

OCA — Wed, 16 Sep 2020 07:02:42 GMT

←Older revision		Revision as of 07:02, 16 September 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7k03 is ON HOLD	+	The entry 7k03 is ON HOLD until Sep 03 2022

	Authors: Karim, M.R., Schonbrunn, E.		Authors: Karim, M.R., Schonbrunn, E.

OCA: Protected "7k03" [edit=sysop:move=sysop]

OCA — Wed, 09 Sep 2020 07:48:36 GMT

Protected "7k03" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:48, 9 September 2020

OCA: New page: '''Unreleased structure''' The entry 7k03 is ON HOLD Authors: Karim, M.R., Schonbrunn, E. Description: Crystal structure of the tandem bromodomain (BD1 and BD2) of human TAF1 bound to ...

OCA — Wed, 09 Sep 2020 07:48:33 GMT

New page: '''Unreleased structure''' The entry 7k03 is ON HOLD Authors: Karim, M.R., Schonbrunn, E. Description: Crystal structure of the tandem bromodomain (BD1 and BD2) of human TAF1 bound to ...

New page

'''Unreleased structure'''

The entry 7k03 is ON HOLD

Authors: Karim, M.R., Schonbrunn, E.

Description: Crystal structure of the tandem bromodomain (BD1 and BD2) of human TAF1 bound to ATR kinase inhibitor AZD6738
[[Category: Unreleased Structures]]
[[Category: Karim, M.R]]
[[Category: Schonbrunn, E]]