5i4v - Revision history

OCA at 08:23, 23 August 2023

OCA — Wed, 23 Aug 2023 08:23:18 GMT

←Older revision		Revision as of 08:23, 23 August 2023
Line 3:		Line 3:
	<StructureSection load='5i4v' size='340' side='right'caption='[[5i4v]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='5i4v' size='340' side='right'caption='[[5i4v]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i4v]] is a 4 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=5I4V OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5I4V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i4v]] 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=5I4V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I4V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=67S:{2-[(2R)-4-[4-(HYDROXYMETHYL)-3-(METHYLSULFONYL)PHENYL]-2-(PROPAN-2-YL)PIPERAZIN-1-YL]-4-(TRIFLUOROMETHYL)PYRIMIDIN-5-YL}METHANOL'>67S</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]] 2.61Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NCOA2, BHLHE75, SRC2, TIF2 ([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=67S:{2-[(2R)-4-[4-(HYDROXYMETHYL)-3-(METHYLSULFONYL)PHENYL]-2-(PROPAN-2-YL)PIPERAZIN-1-YL]-4-(TRIFLUOROMETHYL)PYRIMIDIN-5-YL}METHANOL'>67S</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=5i4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i4v OCA], [~~http~~://pdbe.org/5i4v PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5i4v RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5i4v PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5i4v 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=5i4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i4v OCA], [https://pdbe.org/5i4v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i4v RCSB], [https://www.ebi.ac.uk/pdbsum/5i4v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i4v ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN]] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). [~~[http~~://www.uniprot.org/uniprot/~~RXRB_HUMAN RXRB_HUMAN~~]~~] Receptor~~ for ~~retinoic acid. Retinoic acid~~ receptors ~~bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid,~~ and ~~regulate gene expression in various biological processes~~. ~~The RAR/RXR heterodimers bind to~~ the ~~retinoic acid response elements~~ (~~RARE~~) ~~composed~~ of ~~tandem 5'~~-~~AGGTCA-3' sites known as DR1-DR5~~ (~~By similarity). Specifically binds 9-cis retinoic acid (9C~~-RA).	+	[https://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity).[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen, G]]	+	[[Category: Chen G]]
-	[[Category: McKeever~~, B M]]~~	+	[[Category: McKeever BM]]
-	~~[[Category: Agonist]]~~	+
-	~~[[Category: Dna binding protein]]~~	+
-	~~[[Category: Heterodimer]]~~	+
-	~~[[Category: Lxrbeta-lbd]]~~	+
-	~~[[Category: Rxrbeta-lbd~~]]	+

OCA at 07:04, 3 June 2020

OCA — Wed, 03 Jun 2020 07:04:54 GMT

←Older revision		Revision as of 07:04, 3 June 2020
Line 1:		Line 1:

	==Discovery of novel, orally efficacious Liver X Receptor (LXR) beta agonists==		==Discovery of novel, orally efficacious Liver X Receptor (LXR) beta agonists==
-	<StructureSection load='5i4v' size='340' side='right' caption='[[5i4v]], [[Resolution\|resolution]] 2.61Å' scene=''>	+	<StructureSection load='5i4v' size='340' side='right'caption='[[5i4v]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i4v]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I4V OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5I4V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i4v]] is a 4 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=5I4V OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I4V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=67S:{2-[(2R)-4-[4-(HYDROXYMETHYL)-3-(METHYLSULFONYL)PHENYL]-2-(PROPAN-2-YL)PIPERAZIN-1-YL]-4-(TRIFLUOROMETHYL)PYRIMIDIN-5-YL}METHANOL'>67S</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=67S:{2-[(2R)-4-[4-(HYDROXYMETHYL)-3-(METHYLSULFONYL)PHENYL]-2-(PROPAN-2-YL)PIPERAZIN-1-YL]-4-(TRIFLUOROMETHYL)PYRIMIDIN-5-YL}METHANOL'>67S</scene></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=5i4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i4v OCA], [http://pdbe.org/5i4v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i4v RCSB], [http://www.ebi.ac.uk/pdbsum/5i4v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i4v ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NCOA2, BHLHE75, SRC2, TIF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5i4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i4v OCA], [http://pdbe.org/5i4v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i4v RCSB], [http://www.ebi.ac.uk/pdbsum/5i4v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i4v ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5i4v" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5i4v" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Liver X receptor\|Liver X receptor]]
		+	*[[Retinoid X receptor 3D structures\|Retinoid X receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Chen, G]]		[[Category: Chen, G]]
	[[Category: McKeever, B M]]		[[Category: McKeever, B M]]

OCA at 10:24, 13 July 2016

OCA — Wed, 13 Jul 2016 10:24:28 GMT

←Older revision		Revision as of 10:24, 13 July 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5i4v is ~~ON HOLD~~	+	==Discovery of novel, orally efficacious Liver X Receptor (LXR) beta agonists==
		+	<StructureSection load='5i4v' size='340' side='right' caption='[[5i4v]], [[Resolution\|resolution]] 2.61Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5i4v]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I4V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I4V FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=67S:{2-[(2R)-4-[4-(HYDROXYMETHYL)-3-(METHYLSULFONYL)PHENYL]-2-(PROPAN-2-YL)PIPERAZIN-1-YL]-4-(TRIFLUOROMETHYL)PYRIMIDIN-5-YL}METHANOL'>67S</scene></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=5i4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i4v OCA], [http://pdbe.org/5i4v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i4v RCSB], [http://www.ebi.ac.uk/pdbsum/5i4v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i4v ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN]] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). [[http://www.uniprot.org/uniprot/RXRB_HUMAN RXRB_HUMAN]] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	This article describes the application of Contour to the design and discovery of a novel, potent, orally efficacious liver X receptor beta (LXRbeta) agonist (17). Contour technology is a structure-based drug design platform that generates molecules using a context perceptive growth algorithm guided by a contact sensitive scoring function. The growth engine uses binding site perception and programmable growth capability to create drug-like molecules by assembling fragments that naturally complement hydrophilic and hydrophobic features of the protein binding site. Starting with a crystal structure of LXRbeta and a docked 2-(methylsulfonyl)benzyl alcohol fragment (6), Contour was used to design agonists containing a piperazine core. Compound 17 binds to LXRbeta with high affinity and to LXRalpha to a lesser extent, and induces the expression of LXR target genes in vitro and in vivo. This molecule served as a starting point for further optimization and generation of a candidate which is currently in human clinical trials for treating atopic dermatitis.

-	~~Authors~~:	+	Discovery of a Novel, Orally Efficacious Liver X Receptor (LXR) beta Agonist.,Zheng Y, Zhuang L, Fan KY, Tice CM, Zhao W, Dong C, Lotesta SD, Leftheris K, Lindblom PR, Liu Z, Shimada J, Noto PB, Meng S, Hardy A, Howard L, Krosky P, Guo J, Lipinski K, Kandpal G, Bukhtiyarov Y, Zhao Y, Lala D, Van Orden R, Zhou J, Chen G, Wu Z, McKeever BM, McGeehan GM, Gregg RE, Claremon DA, Singh SB J Med Chem. 2016 Apr 14;59(7):3264-71. doi: 10.1021/acs.jmedchem.5b02029. Epub, 2016 Mar 29. PMID:26990539<ref>PMID:26990539</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5i4v" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Chen, G]]
		+	[[Category: McKeever, B M]]
		+	[[Category: Agonist]]
		+	[[Category: Dna binding protein]]
		+	[[Category: Heterodimer]]
		+	[[Category: Lxrbeta-lbd]]
		+	[[Category: Rxrbeta-lbd]]

OCA at 14:09, 15 May 2016

OCA — Sun, 15 May 2016 14:09:49 GMT

←Older revision		Revision as of 14:09, 15 May 2016
Line 3:		Line 3:
	The entry 5i4v is ON HOLD		The entry 5i4v is ON HOLD

-	Authors: ~~Chen, G., McKeever, B.M.~~	+	Authors:

	Description:		Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Chen, G]]
-	[[Category: Mckeever, B.M]]

OCA: Protected "5i4v" [edit=sysop:move=sysop]

OCA — Fri, 26 Feb 2016 16:46:40 GMT

Protected "5i4v" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:46, 26 February 2016

OCA: New page: '''Unreleased structure''' The entry 5i4v is ON HOLD Authors: Chen, G., McKeever, B.M. Description: Category: Unreleased Structures Category: Chen, G [[Category: Mckeever, B.M...

OCA — Fri, 26 Feb 2016 16:46:39 GMT

New page: '''Unreleased structure''' The entry 5i4v is ON HOLD Authors: Chen, G., McKeever, B.M. Description: Category: Unreleased Structures Category: Chen, G [[Category: Mckeever, B.M...

New page

'''Unreleased structure'''

The entry 5i4v is ON HOLD

Authors: Chen, G., McKeever, B.M.

Description:
[[Category: Unreleased Structures]]
[[Category: Chen, G]]
[[Category: Mckeever, B.M]]