6ohu - Revision history

OCA at 14:52, 13 March 2024

OCA — Wed, 13 Mar 2024 14:52:07 GMT

←Older revision		Revision as of 14:52, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6ohu' size='340' side='right'caption='[[6ohu]], [[Resolution\|resolution]] 3.53Å' scene=''>		<StructureSection load='6ohu' size='340' side='right'caption='[[6ohu]], [[Resolution\|resolution]] 3.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ohu]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OHU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6OHU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ohu]] is a 3 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=6OHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OHU FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=CTX:(Z)-2~~-[~~4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY~~]~~-N,N-DIMETHYLETHANAMINE'>CTX</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]] 3.526Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Cholestenol_Delta~~-~~isomerase Cholestenol Delta~~-~~isomerase~~], ~~with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=5.3.3.5 5.3.3.5]~~ </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTX:(Z)-2-[4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY]-N,N-DIMETHYLETHANAMINE'>CTX</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=6ohu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ohu OCA], [~~http~~://pdbe.org/6ohu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ohu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ohu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ohu 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=6ohu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ohu OCA], [https://pdbe.org/6ohu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ohu RCSB], [https://www.ebi.ac.uk/pdbsum/6ohu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ohu ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN]] MEND syndrome;X-linked dominant chondrodysplasia punctata. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.	+	[https://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN] MEND syndrome;X-linked dominant chondrodysplasia punctata. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN]] Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.<ref>PMID:12760743</ref> <ref>PMID:8798407</ref> <ref>PMID:9894009</ref>	+	[https://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN] Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.<ref>PMID:12760743</ref> <ref>PMID:8798407</ref> <ref>PMID:9894009</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	3-beta-hydroxysteroid-Delta(8), Delta(7)-isomerase, known as Emopamil-Binding Protein (EBP), is an endoplasmic reticulum membrane protein involved in cholesterol biosynthesis, autophagy, oligodendrocyte formation. The mutation on EBP can cause Conradi-Hunermann syndrome, an inborn error. Interestingly, EBP binds an abundance of structurally diverse pharmacologically active compounds, causing drug resistance. Here, we report two crystal structures of human EBP, one in complex with the anti-breast cancer drug tamoxifen and the other in complex with the cholesterol biosynthesis inhibitor U18666A. EBP adopts an unreported fold involving five transmembrane-helices (TMs) that creates a membrane cavity presenting a pharmacological binding site that accommodates multiple different ligands. The compounds exploit their positively-charged amine group to mimic the carbocationic sterol intermediate. Mutagenesis studies on specific residues abolish the isomerase activity and decrease the multidrug binding capacity. This work reveals the catalytic mechanism of EBP-mediated isomerization in cholesterol biosynthesis and how this protein may act as a multi-drug binder.	+
-		+
-	Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition.,Long T, Hassan A, Thompson BM, McDonald JG, Wang J, Li X Nat Commun. 2019 Jun 5;10(1):2452. doi: 10.1038/s41467-019-10279-w. PMID:31165728<ref>PMID:31165728</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6ohu" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Cholestenol Delta-isomerase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Li, X]]	+	[[Category: Li X]]
-	[[Category: Long, T]]	+	[[Category: Long T]]
-	~~[[Category: Isomerase]]~~	+
-	~~[[Category: Isomerase-inhibitor complex]]~~	+
-	~~[[Category: Membrane protein~~]]	+

OCA at 06:09, 19 June 2019

OCA — Wed, 19 Jun 2019 06:09:11 GMT

←Older revision		Revision as of 06:09, 19 June 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~6ohu~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of EBP and tamoxifen==
		+	<StructureSection load='6ohu' size='340' side='right'caption='[[6ohu]], [[Resolution\|resolution]] 3.53Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ohu]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OHU FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CTX:(Z)-2-[4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY]-N,N-DIMETHYLETHANAMINE'>CTX</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cholestenol_Delta-isomerase Cholestenol Delta-isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.3.5 5.3.3.5] </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=6ohu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ohu OCA], [http://pdbe.org/6ohu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ohu RCSB], [http://www.ebi.ac.uk/pdbsum/6ohu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ohu ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN]] MEND syndrome;X-linked dominant chondrodysplasia punctata. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN]] Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.<ref>PMID:12760743</ref> <ref>PMID:8798407</ref> <ref>PMID:9894009</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	3-beta-hydroxysteroid-Delta(8), Delta(7)-isomerase, known as Emopamil-Binding Protein (EBP), is an endoplasmic reticulum membrane protein involved in cholesterol biosynthesis, autophagy, oligodendrocyte formation. The mutation on EBP can cause Conradi-Hunermann syndrome, an inborn error. Interestingly, EBP binds an abundance of structurally diverse pharmacologically active compounds, causing drug resistance. Here, we report two crystal structures of human EBP, one in complex with the anti-breast cancer drug tamoxifen and the other in complex with the cholesterol biosynthesis inhibitor U18666A. EBP adopts an unreported fold involving five transmembrane-helices (TMs) that creates a membrane cavity presenting a pharmacological binding site that accommodates multiple different ligands. The compounds exploit their positively-charged amine group to mimic the carbocationic sterol intermediate. Mutagenesis studies on specific residues abolish the isomerase activity and decrease the multidrug binding capacity. This work reveals the catalytic mechanism of EBP-mediated isomerization in cholesterol biosynthesis and how this protein may act as a multi-drug binder.

-	~~Authors~~:	+	Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition.,Long T, Hassan A, Thompson BM, McDonald JG, Wang J, Li X Nat Commun. 2019 Jun 5;10(1):2452. doi: 10.1038/s41467-019-10279-w. PMID:31165728<ref>PMID:31165728</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6ohu" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cholestenol Delta-isomerase]]
		+	[[Category: Large Structures]]
		+	[[Category: Li, X]]
		+	[[Category: Long, T]]
		+	[[Category: Isomerase]]
		+	[[Category: Isomerase-inhibitor complex]]
		+	[[Category: Membrane protein]]

OCA at 07:06, 1 May 2019

OCA — Wed, 01 May 2019 07:06:45 GMT

←Older revision		Revision as of 07:06, 1 May 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ohu is ON HOLD	+	The entry 6ohu is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 17 Apr 2019 04:11:11 GMT

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

←Older revision

Revision as of 04:11, 17 April 2019

OCA: New page: '''Unreleased structure''' The entry 6ohu is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 17 Apr 2019 04:11:09 GMT

New page: '''Unreleased structure''' The entry 6ohu is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6ohu is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]