6axq - Revision history

OCA at 14:28, 4 October 2023

OCA — Wed, 04 Oct 2023 14:28:10 GMT

←Older revision		Revision as of 14:28, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6axq' size='340' side='right'caption='[[6axq]], [[Resolution\|resolution]] 1.30Å' scene=''>		<StructureSection load='6axq' size='340' side='right'caption='[[6axq]], [[Resolution\|resolution]] 1.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6axq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AXQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6AXQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6axq]] is a 4 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=6AXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AXQ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=C2Y:methyl+1H-indole~~-3~~-carboxylate'>C2Y</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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]] 1.3Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[6ay3\|6ay3]], [[6ay5\|6ay5]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C2Y:methyl+1H-indole-3-carboxylate'>C2Y</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
-	~~<tr~~ id~~='activity'><td class~~="~~sblockLbl~~"><~~b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48]~~ </~~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=6axq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6axq OCA], [https://pdbe.org/6axq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6axq RCSB], [https://www.ebi.ac.uk/pdbsum/6axq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6axq ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6axq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6axq OCA], [~~http~~://pdbe.org/6axq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6axq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6axq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6axq ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN]] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:[~~http~~://omim.org/entry/180849 180849]]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.<ref>PMID:11331617</ref> <ref>PMID:12114483</ref> <ref>PMID:12566391</ref> <ref>PMID:15706485</ref>	+	[https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:[https://omim.org/entry/180849 180849]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.<ref>PMID:11331617</ref> <ref>PMID:12114483</ref> <ref>PMID:12566391</ref> <ref>PMID:15706485</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN]] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref>	+	[https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Histone acetyltransferase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Jayaram, H]]	+	[[Category: Jayaram H]]
-	[[Category: Murray~~, J M]]~~	+	[[Category: Murray JM]]
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Crebbp]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 21:33, 28 October 2020

OCA — Wed, 28 Oct 2020 21:33:53 GMT

←Older revision		Revision as of 21:33, 28 October 2020
Line 1:		Line 1:

	==CREBBP bromodomain in complex with Cpd6 (methyl 1H-indole-3-carboxylate)==		==CREBBP bromodomain in complex with Cpd6 (methyl 1H-indole-3-carboxylate)==
-	<StructureSection load='6axq' size='340' side='right' caption='[[6axq]], [[Resolution\|resolution]] 1.30Å' scene=''>	+	<StructureSection load='6axq' size='340' side='right'caption='[[6axq]], [[Resolution\|resolution]] 1.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6axq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AXQ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AXQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6axq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AXQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6AXQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C2Y:methyl+1H-indole-3-carboxylate'>C2Y</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C2Y:methyl+1H-indole-3-carboxylate'>C2Y</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ay3\|6ay3]], [[6ay5\|6ay5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ay3\|6ay3]], [[6ay5\|6ay5]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></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=6axq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6axq OCA], [http://pdbe.org/6axq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6axq RCSB], [http://www.ebi.ac.uk/pdbsum/6axq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6axq ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6axq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6axq OCA], [http://pdbe.org/6axq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6axq RCSB], [http://www.ebi.ac.uk/pdbsum/6axq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6axq ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 6axq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6axq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[CREB-binding protein 3D structures\|CREB-binding protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
		+	[[Category: Large Structures]]
	[[Category: Jayaram, H]]		[[Category: Jayaram, H]]
	[[Category: Murray, J M]]		[[Category: Murray, J M]]

OCA at 07:24, 22 February 2018

OCA — Thu, 22 Feb 2018 07:24:48 GMT

←Older revision		Revision as of 07:24, 22 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6axq is ~~ON HOLD~~	+	==CREBBP bromodomain in complex with Cpd6 (methyl 1H-indole-3-carboxylate)==
		+	<StructureSection load='6axq' size='340' side='right' caption='[[6axq]], [[Resolution\|resolution]] 1.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6axq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AXQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AXQ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C2Y:methyl+1H-indole-3-carboxylate'>C2Y</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ay3\|6ay3]], [[6ay5\|6ay5]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></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=6axq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6axq OCA], [http://pdbe.org/6axq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6axq RCSB], [http://www.ebi.ac.uk/pdbsum/6axq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6axq ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN]] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:[http://omim.org/entry/180849 180849]]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.<ref>PMID:11331617</ref> <ref>PMID:12114483</ref> <ref>PMID:12566391</ref> <ref>PMID:15706485</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN]] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we disclosed the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region and then building into the LPF shelf. Herein, we report the "hybridization" of a variety of KAc-binding fragments with a tetrahydroquinoline scaffold that makes optimal interactions with the LPF shelf, imparting enhanced potency and selectivity to the hybridized ligand. To demonstrate the utility of our hybridization approach, two analogues containing unique Asn binders and the optimized tetrahydroquinoline moiety were rapidly optimized to yield single-digit nanomolar inhibitors of CBP with exquisite selectivity over BRD4(1) and the broader bromodomain family.

-	~~Authors:~~ Murray, J.M., ~~Jayaram, H~~.	+	A Unique Approach to Design Potent and Selective Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP) Inhibitors.,Bronner SM, Murray J, Romero FA, Lai KW, Tsui V, Cyr P, Beresini MH, de Leon Boenig G, Chen Z, Choo EF, Clark KR, Crawford TD, Jayaram H, Kaufman S, Li R, Li Y, Liao J, Liang X, Liu W, Ly J, Maher J, Wai J, Wang F, Zheng A, Zhu X, Magnuson S J Med Chem. 2017 Dec 28;60(24):10151-10171. doi: 10.1021/acs.jmedchem.7b01372., Epub 2017 Dec 11. PMID:29155580<ref>PMID:29155580</ref>

-	~~Description: CREBBP bromodomain in complex with Cpd6 (methyl 1H~~-~~indole~~-~~3-carboxylate)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Murray, J.M~~]]	+	<div class="pdbe-citations 6axq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Histone acetyltransferase]]
	[[Category: Jayaram, H]]		[[Category: Jayaram, H]]
		+	[[Category: Murray, J M]]
		+	[[Category: Bromodomain]]
		+	[[Category: Crebbp]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "6axq" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 16:56:04 GMT

Protected "6axq" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:56, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6axq is ON HOLD Authors: Murray, J.M., Jayaram, H. Description: CREBBP bromodomain in complex with Cpd6 (methyl 1H-indole-3-carboxylate) [[Category...

OCA — Wed, 27 Sep 2017 16:56:03 GMT

New page: '''Unreleased structure''' The entry 6axq is ON HOLD Authors: Murray, J.M., Jayaram, H. Description: CREBBP bromodomain in complex with Cpd6 (methyl 1H-indole-3-carboxylate) [[Category...

New page

'''Unreleased structure'''

The entry 6axq is ON HOLD

Authors: Murray, J.M., Jayaram, H.

Description: CREBBP bromodomain in complex with Cpd6 (methyl 1H-indole-3-carboxylate)
[[Category: Unreleased Structures]]
[[Category: Murray, J.M]]
[[Category: Jayaram, H]]