5lz5 - Revision history

OCA at 18:16, 1 November 2023

OCA — Wed, 01 Nov 2023 18:16:41 GMT

←Older revision		Revision as of 18:16, 1 November 2023
Line 3:		Line 3:
	<StructureSection load='5lz5' size='340' side='right'caption='[[5lz5]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='5lz5' size='340' side='right'caption='[[5lz5]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5lz5]] is a 1 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=5LZ5 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5LZ5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5lz5]] is a 1 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=5LZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LZ5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7K4:2-FLUORANYL-5-[2-[(4~{S})-4-METHYL-2-OXIDANYLIDENE-4-PHENYL-PYRROLIDIN-1-YL]ETHOXY]BENZENECARBONITRILE'>7K4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.05Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PLA2G7, PAFAH ([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=7K4:2-FLUORANYL-5-[2-[(4~{S})-4-METHYL-2-OXIDANYLIDENE-4-PHENYL-PYRROLIDIN-1-YL]ETHOXY]BENZENECARBONITRILE'>7K4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-alkyl-2-acetylglycerophosphocholine_esterase 1-alkyl-2-acetylglycerophosphocholine esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.47 3.1.1.47] </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=5lz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lz5 OCA], [https://pdbe.org/5lz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lz5 RCSB], [https://www.ebi.ac.uk/pdbsum/5lz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lz5 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=5lz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lz5 OCA], [~~http~~://pdbe.org/5lz5 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5lz5 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5lz5 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5lz5 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/PAFA_HUMAN PAFA_HUMAN]] Defects in PLA2G7 are the cause of platelet-activating factor acetylhydrolase deficiency (PAFAD) [MIM:[~~http~~://omim.org/entry/614278 614278]]. An enzymatic deficiency that results in exacerbated bodily response to inflammatory agents. Asthmatic individuals affected by this condition may manifest severe respiratory symptoms.<ref>PMID:8675689</ref> <ref>PMID:9245731</ref> <ref>PMID:9412624</ref> <ref>PMID:9472966</ref> <ref>PMID:9759612</ref> Defects in PLA2G7 are a cause of susceptibility to asthma (ASTHMA) [MIM:[~~http~~://omim.org/entry/600807 600807]]. The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi. Note=PLA2G7 variants can be a risk factor for the development of asthma and PLA2G7 may act as a modifier gene that modulates the severity of this disease.<ref>PMID:10733466</ref> Defects in PLA2G7 are a cause of susceptibility to atopic hypersensitivity (ATOPY) [MIM:[~~http~~://omim.org/entry/147050 147050]]. A condition characterized by predisposition to develop hypersensitivity reactions. Atopic individuals can develop eczema, allergic rhinitis and allergic asthma.<ref>PMID:10733466</ref>	+	[https://www.uniprot.org/uniprot/PAFA_HUMAN PAFA_HUMAN] Defects in PLA2G7 are the cause of platelet-activating factor acetylhydrolase deficiency (PAFAD) [MIM:[https://omim.org/entry/614278 614278]. An enzymatic deficiency that results in exacerbated bodily response to inflammatory agents. Asthmatic individuals affected by this condition may manifest severe respiratory symptoms.<ref>PMID:8675689</ref> <ref>PMID:9245731</ref> <ref>PMID:9412624</ref> <ref>PMID:9472966</ref> <ref>PMID:9759612</ref> Defects in PLA2G7 are a cause of susceptibility to asthma (ASTHMA) [MIM:[https://omim.org/entry/600807 600807]. The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi. Note=PLA2G7 variants can be a risk factor for the development of asthma and PLA2G7 may act as a modifier gene that modulates the severity of this disease.<ref>PMID:10733466</ref> Defects in PLA2G7 are a cause of susceptibility to atopic hypersensitivity (ATOPY) [MIM:[https://omim.org/entry/147050 147050]. A condition characterized by predisposition to develop hypersensitivity reactions. Atopic individuals can develop eczema, allergic rhinitis and allergic asthma.<ref>PMID:10733466</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PAFA_HUMAN PAFA_HUMAN]] Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. Has a specificity for substrates with a short residue at the sn-2 position. It is inactive against long-chain phospholipids.	+	[https://www.uniprot.org/uniprot/PAFA_HUMAN PAFA_HUMAN] Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. Has a specificity for substrates with a short residue at the sn-2 position. It is inactive against long-chain phospholipids.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~1-alkyl-2-acetylglycerophosphocholine esterase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Day~~, P J~~]]	+	[[Category: Day PJ]]
-	[[Category: Woolford~~, A J.A]]~~	+	[[Category: Woolford AJA]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Lipid metabolism]]~~	+
-	~~[[Category: Lp-pla2 phospholipase]]~~	+
-	~~[[Category: Lp-pla2#4~~]]	+

OCA at 10:56, 12 August 2020

OCA — Wed, 12 Aug 2020 10:56:10 GMT

←Older revision		Revision as of 10:56, 12 August 2020
Line 1:		Line 1:

	==Fragment-based inhibitors of Lipoprotein associated Phospholipase A2==		==Fragment-based inhibitors of Lipoprotein associated Phospholipase A2==
-	<StructureSection load='5lz5' size='340' side='right' caption='[[5lz5]], [[Resolution\|resolution]] 2.05Å' scene=''>	+	<StructureSection load='5lz5' size='340' side='right'caption='[[5lz5]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5lz5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LZ5 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5LZ5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5lz5]] is a 1 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=5LZ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LZ5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7K4:2-FLUORANYL-5-[2-[(4~{S})-4-METHYL-2-OXIDANYLIDENE-4-PHENYL-PYRROLIDIN-1-YL]ETHOXY]BENZENECARBONITRILE'>7K4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7K4:2-FLUORANYL-5-[2-[(4~{S})-4-METHYL-2-OXIDANYLIDENE-4-PHENYL-PYRROLIDIN-1-YL]ETHOXY]BENZENECARBONITRILE'>7K4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PLA2G7, PAFAH ([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/1-alkyl-2-acetylglycerophosphocholine_esterase 1-alkyl-2-acetylglycerophosphocholine esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.47 3.1.1.47] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-alkyl-2-acetylglycerophosphocholine_esterase 1-alkyl-2-acetylglycerophosphocholine esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.47 3.1.1.47] </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=5lz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lz5 OCA], [http://pdbe.org/5lz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lz5 RCSB], [http://www.ebi.ac.uk/pdbsum/5lz5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lz5 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=5lz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lz5 OCA], [http://pdbe.org/5lz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lz5 RCSB], [http://www.ebi.ac.uk/pdbsum/5lz5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lz5 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5lz5" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5lz5" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phospholipase A2 3D structures\|Phospholipase A2 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: 1-alkyl-2-acetylglycerophosphocholine esterase]]		[[Category: 1-alkyl-2-acetylglycerophosphocholine esterase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Day, P J]]		[[Category: Day, P J]]
	[[Category: Woolford, A J.A]]		[[Category: Woolford, A J.A]]

OCA at 21:33, 22 December 2016

OCA — Thu, 22 Dec 2016 21:33:01 GMT

←Older revision		Revision as of 21:33, 22 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5lz5 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Fragment-based inhibitors of Lipoprotein associated Phospholipase A2==
		+	<StructureSection load='5lz5' size='340' side='right' caption='[[5lz5]], [[Resolution\|resolution]] 2.05Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5lz5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LZ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LZ5 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7K4:2-FLUORANYL-5-[2-[(4~{S})-4-METHYL-2-OXIDANYLIDENE-4-PHENYL-PYRROLIDIN-1-YL]ETHOXY]BENZENECARBONITRILE'>7K4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-alkyl-2-acetylglycerophosphocholine_esterase 1-alkyl-2-acetylglycerophosphocholine esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.47 3.1.1.47] </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=5lz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lz5 OCA], [http://pdbe.org/5lz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lz5 RCSB], [http://www.ebi.ac.uk/pdbsum/5lz5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lz5 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PAFA_HUMAN PAFA_HUMAN]] Defects in PLA2G7 are the cause of platelet-activating factor acetylhydrolase deficiency (PAFAD) [MIM:[http://omim.org/entry/614278 614278]]. An enzymatic deficiency that results in exacerbated bodily response to inflammatory agents. Asthmatic individuals affected by this condition may manifest severe respiratory symptoms.<ref>PMID:8675689</ref> <ref>PMID:9245731</ref> <ref>PMID:9412624</ref> <ref>PMID:9472966</ref> <ref>PMID:9759612</ref> Defects in PLA2G7 are a cause of susceptibility to asthma (ASTHMA) [MIM:[http://omim.org/entry/600807 600807]]. The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi. Note=PLA2G7 variants can be a risk factor for the development of asthma and PLA2G7 may act as a modifier gene that modulates the severity of this disease.<ref>PMID:10733466</ref> Defects in PLA2G7 are a cause of susceptibility to atopic hypersensitivity (ATOPY) [MIM:[http://omim.org/entry/147050 147050]]. A condition characterized by predisposition to develop hypersensitivity reactions. Atopic individuals can develop eczema, allergic rhinitis and allergic asthma.<ref>PMID:10733466</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PAFA_HUMAN PAFA_HUMAN]] Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. Has a specificity for substrates with a short residue at the sn-2 position. It is inactive against long-chain phospholipids.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Lp-PLA2 has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery of a new fragment derived chemotype that interacts with the active site of Lp-PLA2. The starting fragment hit was discovered through an X-ray fragment screen and showed no activity in the bioassay (IC50 > 1 mM). The fragment hit was optimized using a variety of structure-based drug design techniques, including virtual screening, fragment merging, and improvement of shape complementarity. A novel series of Lp-PLA2 inhibitors was generated with low lipophilicity and a promising pharmacokinetic profile.

-	~~Authors: Woolford, A.J.A~~., Day, P.J.	+	Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2).,Woolford AJ, Day PJ, Beneton V, Berdini V, Coyle JE, Dudit Y, Grondin P, Huet P, Lee LY, Manas ES, McMenamin RL, Murray CW, Page LW, Patel VK, Potvain F, Rich SJ, Sang Y, Somers DO, Trottet L, Wan Z, Zhang X J Med Chem. 2016 Dec 8;59(23):10738-10749. Epub 2016 Nov 18. PMID:27933945<ref>PMID:27933945</ref>

-	~~Description: Fragment-based inhibitors~~ of ~~Lipoprotein associated Phospholipase A2~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Day, P.J]]	+	<div class="pdbe-citations 5lz5" style="background-color:#fffaf0;"></div>
-	[[Category: Woolford, A.J.A]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: 1-alkyl-2-acetylglycerophosphocholine esterase]]
		+	[[Category: Day, P J]]
		+	[[Category: Woolford, A J.A]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Lipid metabolism]]
		+	[[Category: Lp-pla2 phospholipase]]
		+	[[Category: Lp-pla2#4]]

OCA at 15:49, 2 November 2016

OCA — Wed, 02 Nov 2016 15:49:14 GMT

←Older revision		Revision as of 15:49, 2 November 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5lz5 is ON HOLD	+	The entry 5lz5 is ON HOLD until Paper Publication

-	Authors: Woolford, A.J.-A., Day, P.J.	+	Authors: Woolford, A.J.A., Day, P.J.

	Description: Fragment-based inhibitors of Lipoprotein associated Phospholipase A2		Description: Fragment-based inhibitors of Lipoprotein associated Phospholipase A2
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Day, P.J]]		[[Category: Day, P.J]]
-	[[Category: Woolford, A.J.-A]]	+	[[Category: Woolford, A.J.A]]

OCA: Protected "5lz5" [edit=sysop:move=sysop]

OCA — Wed, 05 Oct 2016 19:23:44 GMT

Protected "5lz5" [edit=sysop:move=sysop]

←Older revision

Revision as of 19:23, 5 October 2016

OCA: New page: '''Unreleased structure''' The entry 5lz5 is ON HOLD Authors: Woolford, A.J.-A., Day, P.J. Description: Fragment-based inhibitors of Lipoprotein associated Phospholipase A2 [[Category:...

OCA — Wed, 05 Oct 2016 19:23:43 GMT

New page: '''Unreleased structure''' The entry 5lz5 is ON HOLD Authors: Woolford, A.J.-A., Day, P.J. Description: Fragment-based inhibitors of Lipoprotein associated Phospholipase A2 [[Category:...

New page

'''Unreleased structure'''

The entry 5lz5 is ON HOLD

Authors: Woolford, A.J.-A., Day, P.J.

Description: Fragment-based inhibitors of Lipoprotein associated Phospholipase A2
[[Category: Unreleased Structures]]
[[Category: Day, P.J]]
[[Category: Woolford, A.J.-A]]