5nu5 - Revision history

OCA at 12:08, 22 November 2023

OCA — Wed, 22 Nov 2023 12:08:04 GMT

←Older revision		Revision as of 12:08, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='5nu5' size='340' side='right'caption='[[5nu5]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='5nu5' size='340' side='right'caption='[[5nu5]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nu5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NU5 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5NU5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nu5]] is a 2 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=5NU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NU5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=99E:~{N}-[[2,8-bis(oxidanyl)naphthalen-1-yl]methyl]-4-ethanoyl-3-ethyl-5-methyl-1~{H}-pyrrole-2-carboxamide'>99E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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='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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=99E:~{N}-[[2,8-bis(oxidanyl)naphthalen-1-yl]methyl]-4-ethanoyl-3-ethyl-5-methyl-1~{H}-pyrrole-2-carboxamide'>99E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=5nu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nu5 OCA], [~~http~~://pdbe.org/5nu5 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nu5 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nu5 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nu5 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=5nu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nu5 OCA], [https://pdbe.org/5nu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nu5 RCSB], [https://www.ebi.ac.uk/pdbsum/5nu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nu5 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 28:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Histone acetyltransferase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Huegle, M]]	+	[[Category: Huegle M]]
-	[[Category: Wohlwend, D]]	+	[[Category: Wohlwend D]]
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Ep300]]~~	+
-	~~[[Category: Epigenetic]]~~	+
-	~~[[Category: Protein-inhibitor complex]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 12:12, 26 August 2020

OCA — Wed, 26 Aug 2020 12:12:18 GMT

←Older revision		Revision as of 12:12, 26 August 2020
Line 1:		Line 1:

	==Crystal structure of the human bromodomain of EP300 bound to the inhibitor XDM-CBP==		==Crystal structure of the human bromodomain of EP300 bound to the inhibitor XDM-CBP==
-	<StructureSection load='5nu5' size='340' side='right' caption='[[5nu5]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='5nu5' size='340' side='right'caption='[[5nu5]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nu5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NU5 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NU5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nu5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NU5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NU5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=99E:~{N}-[[2,8-bis(oxidanyl)naphthalen-1-yl]methyl]-4-ethanoyl-3-ethyl-5-methyl-1~{H}-pyrrole-2-carboxamide'>99E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=99E:~{N}-[[2,8-bis(oxidanyl)naphthalen-1-yl]methyl]-4-ethanoyl-3-ethyl-5-methyl-1~{H}-pyrrole-2-carboxamide'>99E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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='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=5nu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nu5 OCA], [http://pdbe.org/5nu5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nu5 RCSB], [http://www.ebi.ac.uk/pdbsum/5nu5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nu5 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=5nu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nu5 OCA], [http://pdbe.org/5nu5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nu5 RCSB], [http://www.ebi.ac.uk/pdbsum/5nu5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nu5 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5nu5" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5nu5" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone acetyltransferase 3D structures\|Histone acetyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
		+	[[Category: Large Structures]]
	[[Category: Huegle, M]]		[[Category: Huegle, M]]
	[[Category: Wohlwend, D]]		[[Category: Wohlwend, D]]

OCA at 05:58, 17 August 2017

OCA — Thu, 17 Aug 2017 05:58:56 GMT

←Older revision		Revision as of 05:58, 17 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5nu5 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the human bromodomain of EP300 bound to the inhibitor XDM-CBP==
		+	<StructureSection load='5nu5' size='340' side='right' caption='[[5nu5]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5nu5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NU5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NU5 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=99E:~{N}-[[2,8-bis(oxidanyl)naphthalen-1-yl]methyl]-4-ethanoyl-3-ethyl-5-methyl-1~{H}-pyrrole-2-carboxamide'>99E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nu5 OCA], [http://pdbe.org/5nu5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nu5 RCSB], [http://www.ebi.ac.uk/pdbsum/5nu5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nu5 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BET bromodomain inhibitors are widely used both as chemical tools to study the biological role of their targets in living organisms, and as candidates for drug development against several cancer variants and human disorders. However, non-BET bromodomains such as those in p300 and CBP are less studied. Here, we introduce XDM-CBP, a highly potent and selective inhibitor for the bromodomains of CBP and p300 derived from a pan-selective BET BRD-binding fragment. In addition to X-ray crystal structure analysis and thermodynamic profiling, we used XDM-CBP in in vitro cell screenings of several cancer cell lines to study its inhibitory potential on cancer cell proliferation. Our results demonstrate that XDM-CBP is a potent and selective CBP/p300 inhibitor that acts on specific cancer cell lines, in particular malignant melanoma, breast cancer, and leukemia.

-	~~Authors~~:	+	Beyond the BET family: targeting CBP/p300 with 4-acyl pyrroles.,Hugle M, Lucas X, Ostrovskyi D, Regenass P, Gerhardt S, Einsle O, Hau M, Jung M, Breit B, Gunther S, Wohlwend D Angew Chem Int Ed Engl. 2017 Aug 2. doi: 10.1002/anie.201705516. PMID:28766825<ref>PMID:28766825</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5nu5" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Histone acetyltransferase]]
		+	[[Category: Huegle, M]]
		+	[[Category: Wohlwend, D]]
		+	[[Category: Bromodomain]]
		+	[[Category: Ep300]]
		+	[[Category: Epigenetic]]
		+	[[Category: Protein-inhibitor complex]]
		+	[[Category: Transferase]]

OCA: Protected "5nu5" [edit=sysop:move=sysop]

OCA — Wed, 10 May 2017 09:21:12 GMT

Protected "5nu5" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:21, 10 May 2017

OCA: New page: '''Unreleased structure''' The entry 5nu5 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 10 May 2017 09:21:11 GMT

New page: '''Unreleased structure''' The entry 5nu5 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5nu5 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]