5syn - Revision history

OCA at 12:51, 4 October 2023

2023-10-04T12:51:16Z

← Older revision		Revision as of 12:51, 4 October 2023
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	<StructureSection load='5syn' size='340' side='right'caption='[[5syn]], [[Resolution\|resolution]] 1.64Å' scene=''>		<StructureSection load='5syn' size='340' side='right'caption='[[5syn]], [[Resolution\|resolution]] 1.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5syn]] 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=5SYN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5SYN FirstGlance]. <br>		<table><tr><td colspan='2'>[[5syn]] 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=5SYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SYN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=71T:2-[4-(4-METHOXYPHENYL)PIPERAZINE-1-CARBONYL]-5LAMBDA~6~-THIENO[3,2-C][1]BENZOTHIOPYRAN-5,5(4H)-DIONE'>71T</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]] 1.64Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5sym\|5sym]]</td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=71T:2-[4-(4-METHOXYPHENYL)PIPERAZINE-1-CARBONYL]-5LAMBDA~6~-THIENO[3,2-C][1]BENZOTHIOPYRAN-5,5(4H)-DIONE'>71T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LYPLA2, APT2 ([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=5syn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syn OCA], [https://pdbe.org/5syn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5syn RCSB], [https://www.ebi.ac.uk/pdbsum/5syn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5syn 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=5syn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syn OCA], [~~http~~://pdbe.org/5syn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5syn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5syn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5syn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/LYPA2_HUMAN LYPA2_HUMAN]] May hydrolyze fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has lysophospholipase activity (By similarity). Deacylates GAP43.<ref>PMID:21152083</ref>		[https://www.uniprot.org/uniprot/LYPA2_HUMAN LYPA2_HUMAN] May hydrolyze fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has lysophospholipase activity (By similarity). Deacylates GAP43.<ref>PMID:21152083</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Thioesterase\|Thioesterase]]		*[[Thioesterase 3D structures\|Thioesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Labby~~, K J~~]]		[[Category: Labby KJ]]
	[[Category: Martin~~, B R~~]]		[[Category: Martin BR]]
	[[Category: Meagher~~, J L~~]]		[[Category: Meagher JL]]
	[[Category: Stuckey~~, J A~~]]		[[Category: Stuckey JA]]
	[[Category: Won~~, S J]]~~		[[Category: Won SJ]]
	~~[[Category: Hydrolase]]~~
	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~
	~~[[Category: Inhibitor]]~~
	~~[[Category: Thioesterase~~]]

OCA at 09:20, 4 December 2019

2019-12-04T09:20:48Z

← Older revision		Revision as of 09:20, 4 December 2019
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	==Cocrystal structure of the human acyl protein thioesterase 2 with an isoform-selective inhibitor, ML349==		==Cocrystal structure of the human acyl protein thioesterase 2 with an isoform-selective inhibitor, ML349==
	<StructureSection load='5syn' size='340' side='right' caption='[[5syn]], [[Resolution\|resolution]] 1.64Å' scene=''>		<StructureSection load='5syn' size='340' side='right'caption='[[5syn]], [[Resolution\|resolution]] 1.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5syn]] 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=5SYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYN FirstGlance]. <br>		<table><tr><td colspan='2'>[[5syn]] 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=5SYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYN FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 5syn" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5syn" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Thioesterase\|Thioesterase]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Labby, K J]]		[[Category: Labby, K J]]
	[[Category: Martin, B R]]		[[Category: Martin, B R]]

OCA at 18:54, 15 November 2017

2017-11-15T18:54:06Z

← Older revision		Revision as of 18:54, 15 November 2017
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	<StructureSection load='5syn' size='340' side='right' caption='[[5syn]], [[Resolution\|resolution]] 1.64Å' scene=''>		<StructureSection load='5syn' size='340' side='right' caption='[[5syn]], [[Resolution\|resolution]] 1.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5syn]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYN FirstGlance]. <br>		<table><tr><td colspan='2'>[[5syn]] 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=5SYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=71T:2-[4-(4-METHOXYPHENYL)PIPERAZINE-1-CARBONYL]-5LAMBDA~6~-THIENO[3,2-C][1]BENZOTHIOPYRAN-5,5(4H)-DIONE'>71T</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"><scene name='pdbligand=71T:2-[4-(4-METHOXYPHENYL)PIPERAZINE-1-CARBONYL]-5LAMBDA~6~-THIENO[3,2-C][1]BENZOTHIOPYRAN-5,5(4H)-DIONE'>71T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5sym\|5sym]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5sym\|5sym]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LYPLA2, APT2 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5syn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syn OCA], [http://pdbe.org/5syn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5syn RCSB], [http://www.ebi.ac.uk/pdbsum/5syn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5syn 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=5syn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syn OCA], [http://pdbe.org/5syn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5syn RCSB], [http://www.ebi.ac.uk/pdbsum/5syn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5syn ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Labby, K J]]		[[Category: Labby, K J]]
	[[Category: Martin, B R]]		[[Category: Martin, B R]]

OCA at 20:09, 9 December 2016

2016-12-09T20:09:26Z

← Older revision		Revision as of 20:09, 9 December 2016
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/LYPA2_HUMAN LYPA2_HUMAN]] May hydrolyze fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has lysophospholipase activity (By similarity). Deacylates GAP43.<ref>PMID:21152083</ref>		[[http://www.uniprot.org/uniprot/LYPA2_HUMAN LYPA2_HUMAN]] May hydrolyze fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has lysophospholipase activity (By similarity). Deacylates GAP43.<ref>PMID:21152083</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Post-translational S-palmitoylation directs the trafficking and membrane localization of hundreds of cellular proteins, often involving a coordinated palmitoylation cycle that requires both protein acyl transferases (PATs) and acyl protein thioesterases (APTs) to actively redistribute S-palmitoylated proteins toward different cellular membrane compartments. This process is necessary for the trafficking and oncogenic signaling of S-palmitoylated Ras isoforms, and potentially many peripheral membrane proteins. The depalmitoylating enzymes APT1 and APT2 are separately conserved in all vertebrates, suggesting unique functional roles for each enzyme. The recent discovery of the APT isoform-selective inhibitors ML348 and ML349 has opened new possibilities to probe the function of each enzyme, yet it remains unclear how each inhibitor achieves orthogonal inhibition. Herein, we report the high-resolution structure of human APT2 in complex with ML349 (1.64 A), as well as the complementary structure of human APT1 bound to ML348 (1.55 A). Although the overall peptide backbone structures are nearly identical, each inhibitor adopts a distinct conformation within each active site. In APT1, the trifluoromethyl group of ML348 is positioned above the catalytic triad, but in APT2, the sulfonyl group of ML349 forms hydrogen bonds with active site resident waters to indirectly engage the catalytic triad and oxyanion hole. Reciprocal mutagenesis and activity profiling revealed several differing residues surrounding the active site that serve as critical gatekeepers for isoform accessibility and dynamics. Structural and biochemical analysis suggests the inhibitors occupy a putative acyl-binding region, establishing the mechanism for isoform-specific inhibition, hydrolysis of acyl substrates, and structural orthogonality important for future probe development.

			Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2).,Won SJ, Davda D, Labby KJ, Hwang SY, Pricer R, Majmudar JD, Armacost KA, Rodriguez LA, Rodriguez CL, Chong FS, Torossian KA, Palakurthi J, Hur ES, Meagher JL, Brooks CL 3rd, Stuckey JA, Martin BR ACS Chem Biol. 2016 Oct 31. PMID:27748579<ref>PMID:27748579</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5syn" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:50, 26 October 2016

2016-10-26T18:50:01Z

← Older revision		Revision as of 18:50, 26 October 2016
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 5syn ~~is ON HOLD until Paper Publication~~		==Cocrystal structure of the human acyl protein thioesterase 2 with an isoform-selective inhibitor, ML349==
			<StructureSection load='5syn' size='340' side='right' caption='[[5syn]], [[Resolution\|resolution]] 1.64Å' scene=''>
	~~Authors~~: ~~Labby, K~~.J., ~~Stuckey~~, J.A., ~~Meagher, J~~.L., ~~Won~~, S.J., ~~Martin~~, B.R.		== Structural highlights ==
			<table><tr><td colspan='2'>[[5syn]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYN FirstGlance]. <br>
	~~Description: Cocrystal structure of the human acyl protein thioesterase 2 with an isoform-selective inhibitor, ML349~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=71T:2-[4-(4-METHOXYPHENYL)PIPERAZINE-1-CARBONYL]-5LAMBDA~6~-THIENO[3,2-C][1]BENZOTHIOPYRAN-5,5(4H)-DIONE'>71T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	[[~~Category~~: ~~Unreleased Structures~~]]		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5sym\|5sym]]</td></tr>
	[[Category: Labby, K.J]]		<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=5syn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syn OCA], [http://pdbe.org/5syn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5syn RCSB], [http://www.ebi.ac.uk/pdbsum/5syn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5syn ProSAT]</span></td></tr>
	[[Category: ~~Won~~, ~~S.J~~]]		</table>
	[[Category: Meagher, J.L]]		== Function ==
	[[Category: Stuckey, J.A]]		[[http://www.uniprot.org/uniprot/LYPA2_HUMAN LYPA2_HUMAN]] May hydrolyze fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has lysophospholipase activity (By similarity). Deacylates GAP43.<ref>PMID:21152083</ref>
	[[Category: ~~Martin~~, ~~B.R~~]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Labby, K J]]
			[[Category: Martin, B R]]
			[[Category: Meagher, J L]]
			[[Category: Stuckey, J A]]
			[[Category: Won, S J]]
			[[Category: Hydrolase]]
			[[Category: Hydrolase-hydrolase inhibitor complex]]
			[[Category: Inhibitor]]
			[[Category: Thioesterase]]

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

2016-09-09T15:25:31Z

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

← Older revision	Revision as of 15:25, 9 September 2016
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5syn is ON HOLD until Paper Publication Authors: Labby, K.J., Stuckey, J.A., Meagher, J.L., Won, S.J., Martin, B.R. Description: Cocrystal structur...

2016-09-09T15:25:29Z

New page: '''Unreleased structure''' The entry 5syn is ON HOLD until Paper Publication Authors: Labby, K.J., Stuckey, J.A., Meagher, J.L., Won, S.J., Martin, B.R. Description: Cocrystal structur...

New page

'''Unreleased structure'''

The entry 5syn is ON HOLD until Paper Publication

Authors: Labby, K.J., Stuckey, J.A., Meagher, J.L., Won, S.J., Martin, B.R.

Description: Cocrystal structure of the human acyl protein thioesterase 2 with an isoform-selective inhibitor, ML349
[[Category: Unreleased Structures]]
[[Category: Labby, K.J]]
[[Category: Won, S.J]]
[[Category: Meagher, J.L]]
[[Category: Stuckey, J.A]]
[[Category: Martin, B.R]]