5kj2 - Revision history

OCA at 10:01, 27 September 2023

OCA — Wed, 27 Sep 2023 10:01:47 GMT

←Older revision		Revision as of 10:01, 27 September 2023
Line 3:		Line 3:
	<StructureSection load='5kj2' size='340' side='right'caption='[[5kj2]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='5kj2' size='340' side='right'caption='[[5kj2]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5kj2]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KJ2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5KJ2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5kj2]] 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=5KJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KJ2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6TF:N-[(4-fluorophenyl)methyl]-2-{(1R)-5-[(methylcarbamoyl)amino]-2,4-dioxo-2,3-dihydro-3H-spiro[indene-1,5-[1,3]oxazolidin]-3-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]acetamide'>6TF</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.95Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EP300, P300 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6TF:N-[(4-fluorophenyl)methyl]-2-{(1R)-5-[(methylcarbamoyl)amino]-2,4-dioxo-2,3-dihydro-3H-spiro[indene-1,5-[1,3]oxazolidin]-3-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]acetamide'>6TF</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5kj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kj2 OCA], [https://pdbe.org/5kj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kj2 RCSB], [https://www.ebi.ac.uk/pdbsum/5kj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kj2 ProSAT]</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=5kj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kj2 OCA], [~~http~~://pdbe.org/5kj2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5kj2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5kj2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5kj2 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://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:[~~http~~://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>	+	[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 ==		== Function ==
-	[~~[http~~://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>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5kj2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5kj2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone acetyltransferase 3D structures\|Histone acetyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Histone acetyltransferase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Edalji~~, R P~~]]	+	[[Category: Edalji RP]]
-	[[Category: Jakob~~, C G~~]]	+	[[Category: Jakob CG]]
-	[[Category: Qiu, W]]	+	[[Category: Qiu W]]
-	[[Category: Sun, C]]	+	[[Category: Sun C]]
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:39, 10 April 2019

OCA — Wed, 10 Apr 2019 07:39:52 GMT

←Older revision		Revision as of 07:39, 10 April 2019
Line 1:		Line 1:

	==The novel p300/CBP inhibitor A-485 uncovers a unique mechanism of action to target AR in castrate resistant prostate cancer==		==The novel p300/CBP inhibitor A-485 uncovers a unique mechanism of action to target AR in castrate resistant prostate cancer==
-	<StructureSection load='5kj2' size='340' side='right' caption='[[5kj2]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='5kj2' size='340' side='right'caption='[[5kj2]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5kj2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KJ2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5kj2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KJ2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6TF:N-[(4-fluorophenyl)methyl]-2-{(1R)-5-[(methylcarbamoyl)amino]-2,4-dioxo-2,3-dihydro-3H-spiro[indene-1,5-[1,3]oxazolidin]-3-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]acetamide'>6TF</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6TF:N-[(4-fluorophenyl)methyl]-2-{(1R)-5-[(methylcarbamoyl)amino]-2,4-dioxo-2,3-dihydro-3H-spiro[indene-1,5-[1,3]oxazolidin]-3-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]acetamide'>6TF</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EP300, P300 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5kj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kj2 OCA], [http://pdbe.org/5kj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kj2 RCSB], [http://www.ebi.ac.uk/pdbsum/5kj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kj2 ProSAT]</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=5kj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kj2 OCA], [http://pdbe.org/5kj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kj2 RCSB], [http://www.ebi.ac.uk/pdbsum/5kj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kj2 ProSAT]</span></td></tr>
Line 12:		Line 13:
	== Function ==		== Function ==
	[[http://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>		[[http://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 ==
		+	The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 A) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.
		+
		+	Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.,Lasko LM, Jakob CG, Edalji RP, Qiu W, Montgomery D, Digiammarino EL, Hansen TM, Risi RM, Frey R, Manaves V, Shaw B, Algire M, Hessler P, Lam LT, Uziel T, Faivre E, Ferguson D, Buchanan FG, Martin RL, Torrent M, Chiang GG, Karukurichi K, Langston JW, Weinert BT, Choudhary C, de Vries P, Van Drie JH, McElligott D, Kesicki E, Marmorstein R, Sun C, Cole PA, Rosenberg SH, Michaelides MR, Lai A, Bromberg KD Nature. 2017 Oct 5;550(7674):128-132. doi: 10.1038/nature24028. Epub 2017 Sep 27. PMID:28953875<ref>PMID:28953875</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5kj2" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
Line 17:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Edalji, R P]]		[[Category: Edalji, R P]]
	[[Category: Jakob, C G]]		[[Category: Jakob, C G]]

OCA at 09:18, 1 November 2017

OCA — Wed, 01 Nov 2017 09:18:39 GMT

←Older revision		Revision as of 09:18, 1 November 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The ~~entry~~ 5kj2 is ~~ON HOLD~~ ~~until Paper Publication~~	+	==The novel p300/CBP inhibitor A-485 uncovers a unique mechanism of action to target AR in castrate resistant prostate cancer==
-		+	<StructureSection load='5kj2' size='340' side='right' caption='[[5kj2]], [[Resolution\|resolution]] 1.95Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5kj2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KJ2 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6TF:N-[(4-fluorophenyl)methyl]-2-{(1R)-5-[(methylcarbamoyl)amino]-2,4-dioxo-2,3-dihydro-3H-spiro[indene-1,5-[1,3]oxazolidin]-3-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]acetamide'>6TF</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=5kj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kj2 OCA], [http://pdbe.org/5kj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kj2 RCSB], [http://www.ebi.ac.uk/pdbsum/5kj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kj2 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://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:[http://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 ==
		+	[[http://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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Histone acetyltransferase]]
		+	[[Category: Edalji, R P]]
		+	[[Category: Jakob, C G]]
		+	[[Category: Qiu, W]]
		+	[[Category: Sun, C]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "5kj2" [edit=sysop:move=sysop]

OCA — Wed, 13 Jul 2016 00:24:54 GMT

Protected "5kj2" [edit=sysop:move=sysop]

←Older revision

Revision as of 00:24, 13 July 2016

OCA: New page: '''Unreleased structure''' The entry 5kj2 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 13 Jul 2016 00:24:52 GMT

New page: '''Unreleased structure''' The entry 5kj2 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

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'''Unreleased structure'''

The entry 5kj2 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]