6c6p - Revision history

OCA at 14:26, 13 March 2024

2024-03-13T14:26:38Z

←Older revision		Revision as of 14:26, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6c6p' size='340' side='right'caption='[[6c6p]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6c6p' size='340' side='right'caption='[[6c6p]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6c6p]] is a 2 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=6C6P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6C6P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6c6p]] 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=6C6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C6P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=EMV:(2E)-N-({3-[([3,3-bithiophen]-5-yl)methoxy]phenyl}methyl)-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine'>EMV</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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]] 2.5Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6c6n\|6c6n]], [[6c6r\|6c6r]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=EMV:(2E)-N-({3-[([3,3-bithiophen]-5-yl)methoxy]phenyl}methyl)-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine'>EMV</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SQLE, ERG1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6c6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c6p OCA], [https://pdbe.org/6c6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c6p RCSB], [https://www.ebi.ac.uk/pdbsum/6c6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c6p ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Squalene_monooxygenase Squalene monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.17 1.14.14.17] </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=6c6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c6p OCA], [~~http~~://pdbe.org/6c6p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6c6p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6c6p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6c6p ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ERG1_HUMAN ERG1_HUMAN]] Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.	+	[https://www.uniprot.org/uniprot/ERG1_HUMAN ERG1_HUMAN] Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Squalene epoxidase (SQLE), also known as squalene monooxygenase, catalyzes the stereospecific conversion of squalene to 2,3(S)-oxidosqualene, a key step in cholesterol biosynthesis. SQLE inhibition is targeted for the treatment of hypercholesteremia, cancer, and fungal infections. However, lack of structure-function understanding has hindered further progression of its inhibitors. We have determined the first three-dimensional high-resolution crystal structures of human SQLE catalytic domain with small molecule inhibitors (2.3 A and 2.5 A). Comparison with its unliganded state (3.0 A) reveals conformational rearrangements upon inhibitor binding, thus allowing deeper interpretation of known structure-activity relationships. We use the human SQLE structure to further understand the specificity of terbinafine, an approved agent targeting fungal SQLE, and to provide the structural insights into terbinafine-resistant mutants encountered in the clinic. Collectively, these findings elucidate the structural basis for the specificity of the epoxidation reaction catalyzed by SQLE and enable further rational development of next-generation inhibitors.	+
-		+
-	Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase.,Padyana AK, Gross S, Jin L, Cianchetta G, Narayanaswamy R, Wang F, Wang R, Fang C, Lv X, Biller SA, Dang L, Mahoney CE, Nagaraja N, Pirman D, Sui Z, Popovici-Muller J, Smolen GA Nat Commun. 2019 Jan 9;10(1):97. doi: 10.1038/s41467-018-07928-x. PMID:30626872<ref>PMID:30626872</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6c6p" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[Epoxidase 3D structures\|Epoxidase 3D structures]]		*[[Epoxidase 3D structures\|Epoxidase 3D structures]]
	*[[Monooxygenase 3D structures\|Monooxygenase 3D structures]]		*[[Monooxygenase 3D structures\|Monooxygenase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Squalene monooxygenase]]~~	+	[[Category: Jin L]]
-	[[Category: Jin, L]]	+	[[Category: Padyana AK]]
-	[[Category: Padyana~~, A K]]~~	+
-	~~[[Category: 3-epoxidase]]~~	+
-	~~[[Category: Cholesterol synthesis pathway]]~~	+
-	~~[[Category: Erg1]]~~	+
-	~~[[Category: Fad-dependent monooxygenase]]~~	+
-	~~[[Category: Flavoprotein]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]~~	+
-	~~[[Category: Sqle]]~~	+
-	~~[[Category: Squalene hydroxylase]]~~	+
-	~~[[Category: Squalene-2~~]]	+

OCA at 08:54, 11 November 2020

2020-11-11T08:54:33Z

←Older revision		Revision as of 08:54, 11 November 2020
Line 1:		Line 1:

	==Human squalene epoxidase (SQLE, squalene monooxygenase) structure with FAD and NB-598==		==Human squalene epoxidase (SQLE, squalene monooxygenase) structure with FAD and NB-598==
-	<StructureSection load='6c6p' size='340' side='right' caption='[[6c6p]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='6c6p' size='340' side='right'caption='[[6c6p]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6c6p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C6P OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6C6P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6c6p]] is a 2 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=6C6P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6C6P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=EMV:(2E)-N-({3-[([3,3-bithiophen]-5-yl)methoxy]phenyl}methyl)-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine'>EMV</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=EMV:(2E)-N-({3-[([3,3-bithiophen]-5-yl)methoxy]phenyl}methyl)-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine'>EMV</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6c6n\|6c6n]], [[6c6r\|6c6r]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6c6n\|6c6n]], [[6c6r\|6c6r]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SQLE, ERG1 ([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/Squalene_monooxygenase Squalene monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.17 1.14.14.17] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Squalene_monooxygenase Squalene monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.17 1.14.14.17] </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=6c6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c6p OCA], [http://pdbe.org/6c6p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c6p RCSB], [http://www.ebi.ac.uk/pdbsum/6c6p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c6p 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=6c6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c6p OCA], [http://pdbe.org/6c6p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c6p RCSB], [http://www.ebi.ac.uk/pdbsum/6c6p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c6p ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/ERG1_HUMAN ERG1_HUMAN]] Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.		[[http://www.uniprot.org/uniprot/ERG1_HUMAN ERG1_HUMAN]] Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Squalene epoxidase (SQLE), also known as squalene monooxygenase, catalyzes the stereospecific conversion of squalene to 2,3(S)-oxidosqualene, a key step in cholesterol biosynthesis. SQLE inhibition is targeted for the treatment of hypercholesteremia, cancer, and fungal infections. However, lack of structure-function understanding has hindered further progression of its inhibitors. We have determined the first three-dimensional high-resolution crystal structures of human SQLE catalytic domain with small molecule inhibitors (2.3 A and 2.5 A). Comparison with its unliganded state (3.0 A) reveals conformational rearrangements upon inhibitor binding, thus allowing deeper interpretation of known structure-activity relationships. We use the human SQLE structure to further understand the specificity of terbinafine, an approved agent targeting fungal SQLE, and to provide the structural insights into terbinafine-resistant mutants encountered in the clinic. Collectively, these findings elucidate the structural basis for the specificity of the epoxidation reaction catalyzed by SQLE and enable further rational development of next-generation inhibitors.
		+
		+	Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase.,Padyana AK, Gross S, Jin L, Cianchetta G, Narayanaswamy R, Wang F, Wang R, Fang C, Lv X, Biller SA, Dang L, Mahoney CE, Nagaraja N, Pirman D, Sui Z, Popovici-Muller J, Smolen GA Nat Commun. 2019 Jan 9;10(1):97. doi: 10.1038/s41467-018-07928-x. PMID:30626872<ref>PMID:30626872</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6c6p" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Epoxidase 3D structures\|Epoxidase 3D structures]]
		+	*[[Monooxygenase 3D structures\|Monooxygenase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Squalene monooxygenase]]		[[Category: Squalene monooxygenase]]
	[[Category: Jin, L]]		[[Category: Jin, L]]

OCA at 12:04, 16 January 2019

2019-01-16T12:04:19Z

←Older revision		Revision as of 12:04, 16 January 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6c6p is ~~ON HOLD until Paper Publication~~	+	==Human squalene epoxidase (SQLE, squalene monooxygenase) structure with FAD and NB-598==
-		+	<StructureSection load='6c6p' size='340' side='right' caption='[[6c6p]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6c6p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C6P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C6P FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=EMV:(2E)-N-({3-[([3,3-bithiophen]-5-yl)methoxy]phenyl}methyl)-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine'>EMV</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6c6n\|6c6n]], [[6c6r\|6c6r]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Squalene_monooxygenase Squalene monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.17 1.14.14.17] </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=6c6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c6p OCA], [http://pdbe.org/6c6p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c6p RCSB], [http://www.ebi.ac.uk/pdbsum/6c6p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c6p ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ERG1_HUMAN ERG1_HUMAN]] Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Squalene monooxygenase]]
		+	[[Category: Jin, L]]
		+	[[Category: Padyana, A K]]
		+	[[Category: 3-epoxidase]]
		+	[[Category: Cholesterol synthesis pathway]]
		+	[[Category: Erg1]]
		+	[[Category: Fad-dependent monooxygenase]]
		+	[[Category: Flavoprotein]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
		+	[[Category: Sqle]]
		+	[[Category: Squalene hydroxylase]]
		+	[[Category: Squalene-2]]

OCA at 06:33, 26 December 2018

2018-12-26T06:33:14Z

←Older revision		Revision as of 06:33, 26 December 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6c6p is ON HOLD	+	The entry 6c6p is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 06:21, 19 December 2018

2018-12-19T06:21:58Z

←Older revision		Revision as of 06:21, 19 December 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6c6p is ON HOLD ~~until Paper Publication~~	+	The entry 6c6p is ON HOLD

-	Authors: ~~Padyana, A.K., Jin, L.~~	+	Authors:

-	Description: ~~Human squalene epoxidase (SQLE, squalene monooxygenase) structure with FAD and NB-598~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Padyana, A.K]]
-	[[Category: Jin, L]]

OCA at 05:02, 12 December 2018

2018-12-12T05:02:29Z

←Older revision		Revision as of 05:02, 12 December 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6c6p is ON HOLD	+	The entry 6c6p is ON HOLD until Paper Publication

	Authors: Padyana, A.K., Jin, L.		Authors: Padyana, A.K., Jin, L.

-	Description: Human squalene epoxidase structure with NB-598	+	Description: Human squalene epoxidase (SQLE, squalene monooxygenase) structure with FAD and NB-598
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Padyana, A.K]]		[[Category: Padyana, A.K]]
	[[Category: Jin, L]]		[[Category: Jin, L]]

OCA at 18:26, 2 December 2018

2018-12-02T18:26:21Z

←Older revision		Revision as of 18:26, 2 December 2018
Line 7:		Line 7:
	Description: Human squalene epoxidase structure with NB-598		Description: Human squalene epoxidase structure with NB-598
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Jin, L]]
	[[Category: Padyana, A.K]]		[[Category: Padyana, A.K]]
		+	[[Category: Jin, L]]

OCA: Protected "6c6p" [edit=sysop:move=sysop]

2018-01-31T04:47:33Z

Protected "6c6p" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:47, 31 January 2018

OCA: New page: '''Unreleased structure''' The entry 6c6p is ON HOLD Authors: Padyana, A.K., Jin, L. Description: Human squalene epoxidase structure with NB-598 Category: Unreleased Structures [[C...

2018-01-31T04:47:32Z

New page: '''Unreleased structure''' The entry 6c6p is ON HOLD Authors: Padyana, A.K., Jin, L. Description: Human squalene epoxidase structure with NB-598 Category: Unreleased Structures [[C...

New page

'''Unreleased structure'''

The entry 6c6p is ON HOLD

Authors: Padyana, A.K., Jin, L.

Description: Human squalene epoxidase structure with NB-598
[[Category: Unreleased Structures]]
[[Category: Jin, L]]
[[Category: Padyana, A.K]]