7szq - Revision history

OCA at 16:56, 18 October 2023

OCA — Wed, 18 Oct 2023 16:56:23 GMT

←Older revision		Revision as of 16:56, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7szq]] 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=7SZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SZQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[7szq]] 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=7SZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SZQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ETL:1-[1-(4-chlorophenyl)cyclopentane-1-carbonyl]-N-1H-pyrazolo[4,3-b]pyridin-5-yl-D-prolinamide'>ETL</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]] 2.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ETL:1-[1-(4-chlorophenyl)cyclopentane-1-carbonyl]-N-1H-pyrazolo[4,3-b]pyridin-5-yl-D-prolinamide'>ETL</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=7szq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7szq OCA], [https://pdbe.org/7szq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7szq RCSB], [https://www.ebi.ac.uk/pdbsum/7szq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7szq 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=7szq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7szq OCA], [https://pdbe.org/7szq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7szq RCSB], [https://www.ebi.ac.uk/pdbsum/7szq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7szq ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7szq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7szq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone acetyltransferase 3D structures\|Histone acetyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:22, 9 November 2022

OCA — Wed, 09 Nov 2022 07:22:14 GMT

←Older revision		Revision as of 07:22, 9 November 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7szq is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human P300 complexed with an azaindazole inhibitor==
		+	<StructureSection load='7szq' size='340' side='right'caption='[[7szq]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7szq]] 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=7SZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SZQ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ETL:1-[1-(4-chlorophenyl)cyclopentane-1-carbonyl]-N-1H-pyrazolo[4,3-b]pyridin-5-yl-D-prolinamide'>ETL</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=7szq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7szq OCA], [https://pdbe.org/7szq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7szq RCSB], [https://www.ebi.ac.uk/pdbsum/7szq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7szq ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN] Note=Defects in EP300 may play a role in epithelial cancer. Note=Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with KAT6A. Defects in EP300 are the cause of Rubinstein-Taybi syndrome type 2 (RSTS2) [MIM:[https://omim.org/entry/613684 613684]. A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients.<ref>PMID:15706485</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN] Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Also functions as acetyltransferase for nonhistone targets. Acetylates 'Lys-131' of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Acetylates FOXO1 and enhances its transcriptional activity.<ref>PMID:11701890</ref> <ref>PMID:10733570</ref> <ref>PMID:11430825</ref> <ref>PMID:12586840</ref> <ref>PMID:12929931</ref> <ref>PMID:15186775</ref> <ref>PMID:15890677</ref> <ref>PMID:16762839</ref> <ref>PMID:18722353</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	E1A binding protein (p300) and CREB binding protein (CBP) are two highly homologous and multidomain histone acetyltransferases. These two proteins are involved in many cellular processes by acting as coactivators of a large number of transcription factors. Dysregulation of p300/CBP has been found in a variety of cancers and other diseases, and inhibition has been shown to decrease Myc expression. Herein, we report the identification of a series of highly potent, proline-based small-molecule p300/CBP histone acetyltransferase (HAT) inhibitors using DNA-encoded library technology in combination with high-throughput screening. The strategy of reducing ChromlogD and fluorination of metabolic soft spots was explored to improve the pharmacokinetic properties of potent p300 inhibitors. Fluorination of both cyclobutyl and proline rings of 22 led to not only reduced clearance but also improved cMyc cellular potency.

-	~~Authors~~:	+	Discovery of Proline-Based p300/CBP Inhibitors Using DNA-Encoded Library Technology in Combination with High-Throughput Screening.,Tian X, Suarez D, Thomson D, Li W, King EA, LaFrance L, Boehm J, Barton L, Di Marco C, Martyr C, Thalji R, Medina J, Knight S, Heerding D, Gao E, Nartey E, Cecconie T, Nixon C, Zhang G, Berrodin TJ, Phelps C, Patel A, Bai X, Lind K, Prabhu N, Messer J, Zhu Z, Shewchuk L, Reid R, Graves AP, McHugh C, Mangatt B J Med Chem. 2022 Oct 27. doi: 10.1021/acs.jmedchem.2c00670. PMID:36302181<ref>PMID:36302181</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7szq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Reid RA]]
		+	[[Category: Shewchuk LM]]

OCA at 05:54, 19 January 2022

OCA — Wed, 19 Jan 2022 05:54:34 GMT

←Older revision		Revision as of 05:54, 19 January 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7szq is ON HOLD	+	The entry 7szq is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 08 Dec 2021 08:35:52 GMT

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

←Older revision

Revision as of 08:35, 8 December 2021

OCA: New page: '''Unreleased structure''' The entry 7szq is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 08 Dec 2021 08:35:51 GMT

New page: '''Unreleased structure''' The entry 7szq is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7szq is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]