5l9z - Revision history

OCA at 16:12, 4 October 2023

OCA — Wed, 04 Oct 2023 16:12:43 GMT

←Older revision		Revision as of 16:12, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5l9z' size='340' side='right'caption='[[5l9z]], [[Resolution\|resolution]] 1.57Å' scene=''>		<StructureSection load='5l9z' size='340' side='right'caption='[[5l9z]], [[Resolution\|resolution]] 1.57Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5l9z]] 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=5L9Z OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5L9Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5l9z]] 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=5L9Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L9Z FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GUX:(1~{R},2~{S},3~{R},4~{S},5~{S},6~{R})-7-[8-[(azanylidene-{4}-azanylidene)amino]octyl]-3,4,5-tris(oxidanyl)-7-azabicyclo[4.1.0]heptane-2-carboxylic+acid'>GUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 1.57Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HPSE, HEP, HPA, HPA1, HPR1, HPSE1, HSE1 ([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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GUX:(1~{R},2~{S},3~{R},4~{S},5~{S},6~{R})-7-[8-[(azanylidene-{4}-azanylidene)amino]octyl]-3,4,5-tris(oxidanyl)-7-azabicyclo[4.1.0]heptane-2-carboxylic+acid'>GUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heparanase Heparanase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.166 3.2.1.166] </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=5l9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l9z OCA], [https://pdbe.org/5l9z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l9z RCSB], [https://www.ebi.ac.uk/pdbsum/5l9z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l9z 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=5l9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l9z OCA], [~~http~~://pdbe.org/5l9z PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5l9z RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5l9z PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5l9z ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/HPSE_HUMAN HPSE_HUMAN]] Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.<ref>PMID:12213822</ref> <ref>PMID:12773484</ref> <ref>PMID:15044433</ref> <ref>PMID:16452201</ref> <ref>PMID:18557927</ref> <ref>PMID:18798279</ref> <ref>PMID:19244131</ref> <ref>PMID:20097882</ref> <ref>PMID:20181948</ref> <ref>PMID:20309870</ref> <ref>PMID:20561914</ref> <ref>PMID:21131364</ref>	+	[https://www.uniprot.org/uniprot/HPSE_HUMAN HPSE_HUMAN] Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.<ref>PMID:12213822</ref> <ref>PMID:12773484</ref> <ref>PMID:15044433</ref> <ref>PMID:16452201</ref> <ref>PMID:18557927</ref> <ref>PMID:18798279</ref> <ref>PMID:19244131</ref> <ref>PMID:20097882</ref> <ref>PMID:20181948</ref> <ref>PMID:20309870</ref> <ref>PMID:20561914</ref> <ref>PMID:21131364</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Heparanase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Davies~~, G J~~]]	+	[[Category: Davies GJ]]
-	[[Category: Jin, Y]]	+	[[Category: Jin Y]]
-	[[Category: Wu, L]]	+	[[Category: Wu L]]
-	~~[[Category: Gh79]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Probe~~]]	+

OCA at 07:39, 23 October 2019

OCA — Wed, 23 Oct 2019 07:39:37 GMT

←Older revision		Revision as of 07:39, 23 October 2019
Line 1:		Line 1:

	==Crystal structure of human heparanase nucleophile mutant (E343Q), in complex with unreacted glucuronic acid configured aziridine probe JJB355==		==Crystal structure of human heparanase nucleophile mutant (E343Q), in complex with unreacted glucuronic acid configured aziridine probe JJB355==
-	<StructureSection load='5l9z' size='340' side='right' caption='[[5l9z]], [[Resolution\|resolution]] 1.57Å' scene=''>	+	<StructureSection load='5l9z' size='340' side='right'caption='[[5l9z]], [[Resolution\|resolution]] 1.57Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5l9z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L9Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5l9z]] 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=5L9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L9Z FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GUX:(1~{R},2~{S},3~{R},4~{S},5~{S},6~{R})-7-[8-[(azanylidene-{4}-azanylidene)amino]octyl]-3,4,5-tris(oxidanyl)-7-azabicyclo[4.1.0]heptane-2-carboxylic+acid'>GUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GUX:(1~{R},2~{S},3~{R},4~{S},5~{S},6~{R})-7-[8-[(azanylidene-{4}-azanylidene)amino]octyl]-3,4,5-tris(oxidanyl)-7-azabicyclo[4.1.0]heptane-2-carboxylic+acid'>GUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HPSE, HEP, HPA, HPA1, HPR1, HPSE1, HSE1 ([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/Heparanase Heparanase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.166 3.2.1.166] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heparanase Heparanase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.166 3.2.1.166] </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=5l9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l9z OCA], [http://pdbe.org/5l9z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l9z RCSB], [http://www.ebi.ac.uk/pdbsum/5l9z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l9z 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=5l9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l9z OCA], [http://pdbe.org/5l9z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l9z RCSB], [http://www.ebi.ac.uk/pdbsum/5l9z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l9z ProSAT]</span></td></tr>
Line 24:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Heparanase]]		[[Category: Heparanase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Davies, G J]]		[[Category: Davies, G J]]
	[[Category: Jin, Y]]		[[Category: Jin, Y]]

OCA at 11:00, 3 August 2017

OCA — Thu, 03 Aug 2017 11:00:36 GMT

←Older revision		Revision as of 11:00, 3 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5l9z is ~~ON HOLD~~	+	==Crystal structure of human heparanase nucleophile mutant (E343Q), in complex with unreacted glucuronic acid configured aziridine probe JJB355==
		+	<StructureSection load='5l9z' size='340' side='right' caption='[[5l9z]], [[Resolution\|resolution]] 1.57Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5l9z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L9Z FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GUX:(1~{R},2~{S},3~{R},4~{S},5~{S},6~{R})-7-[8-[(azanylidene-{4}-azanylidene)amino]octyl]-3,4,5-tris(oxidanyl)-7-azabicyclo[4.1.0]heptane-2-carboxylic+acid'>GUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heparanase Heparanase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.166 3.2.1.166] </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=5l9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l9z OCA], [http://pdbe.org/5l9z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l9z RCSB], [http://www.ebi.ac.uk/pdbsum/5l9z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l9z ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HPSE_HUMAN HPSE_HUMAN]] Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.<ref>PMID:12213822</ref> <ref>PMID:12773484</ref> <ref>PMID:15044433</ref> <ref>PMID:16452201</ref> <ref>PMID:18557927</ref> <ref>PMID:18798279</ref> <ref>PMID:19244131</ref> <ref>PMID:20097882</ref> <ref>PMID:20181948</ref> <ref>PMID:20309870</ref> <ref>PMID:20561914</ref> <ref>PMID:21131364</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Humans express at least two distinct beta-glucuronidase enzymes that are involved in disease: exo-acting beta-glucuronidase (GUSB), whose deficiency gives rise to mucopolysaccharidosis type VII, and endo-acting heparanase (HPSE), whose overexpression is implicated in inflammation and cancers. The medical importance of these enzymes necessitates reliable methods to assay their activities in tissues. Herein, we present a set of beta-glucuronidase-specific activity-based probes (ABPs) that allow rapid and quantitative visualization of GUSB and HPSE in biological samples, providing a powerful tool for dissecting their activities in normal and disease states. Unexpectedly, we find that the supposedly inactive HPSE proenzyme proHPSE is also labeled by our ABPs, leading to surprising insights regarding structural relationships between proHPSE, mature HPSE, and their bacterial homologs. Our results demonstrate the application of beta-glucuronidase ABPs in tracking pathologically relevant enzymes and provide a case study of how ABP-driven approaches can lead to discovery of unanticipated structural and biochemical functionality.

-	~~Authors~~:	+	Activity-based probes for functional interrogation of retaining beta-glucuronidases.,Wu L, Jiang J, Jin Y, Kallemeijn WW, Kuo CL, Artola M, Dai W, van Elk C, van Eijk M, van der Marel GA, Codee JDC, Florea BI, Aerts JMFG, Overkleeft HS, Davies GJ Nat Chem Biol. 2017 Jun 5. doi: 10.1038/nchembio.2395. PMID:28581485<ref>PMID:28581485</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5l9z" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Heparanase]]
		+	[[Category: Davies, G J]]
		+	[[Category: Jin, Y]]
		+	[[Category: Wu, L]]
		+	[[Category: Gh79]]
		+	[[Category: Hydrolase]]
		+	[[Category: Probe]]

OCA: Protected "5l9z" [edit=sysop:move=sysop]

OCA — Thu, 23 Jun 2016 21:54:28 GMT

Protected "5l9z" [edit=sysop:move=sysop]

←Older revision

Revision as of 21:54, 23 June 2016

OCA: New page: '''Unreleased structure''' The entry 5l9z is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 23 Jun 2016 21:54:26 GMT

New page: '''Unreleased structure''' The entry 5l9z is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5l9z is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]