7prt - Revision history

OCA at 13:08, 1 February 2024

OCA — Thu, 01 Feb 2024 13:08:17 GMT

←Older revision		Revision as of 13:08, 1 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7prt]] 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=7PRT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PRT FirstGlance]. <br>		<table><tr><td colspan='2'>[[7prt]] 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=7PRT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PRT FirstGlance]. <br>
-	</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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Z61:2-deoxy-alpha-D-arabino-hexopyranose'>Z61</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]] 1.7Å</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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Z61:2-deoxy-alpha-D-arabino-hexopyranose'>Z61</scene></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=7prt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7prt OCA], [https://pdbe.org/7prt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7prt RCSB], [https://www.ebi.ac.uk/pdbsum/7prt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7prt 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=7prt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7prt OCA], [https://pdbe.org/7prt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7prt RCSB], [https://www.ebi.ac.uk/pdbsum/7prt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7prt ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[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>	+	[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 ==

OCA at 03:10, 8 September 2022

OCA — Thu, 08 Sep 2022 03:10:40 GMT

←Older revision		Revision as of 03:10, 8 September 2022
Line 1:		Line 1:

-	====	+	==Crystal structure of human heparanase in complex with covalent inhibitor CB678==
-	<StructureSection load='7prt' size='340' side='right'caption='[[7prt]]' scene=''>	+	<StructureSection load='7prt' size='340' side='right'caption='[[7prt]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7prt]] 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=7PRT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PRT FirstGlance]. <br>
-	</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=7prt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7prt OCA], [https://pdbe.org/7prt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7prt RCSB], [https://www.ebi.ac.uk/pdbsum/7prt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7prt ProSAT]</span></td></tr>	+	</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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Z61:2-deoxy-alpha-D-arabino-hexopyranose'>Z61</scene></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=7prt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7prt OCA], [https://pdbe.org/7prt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7prt RCSB], [https://www.ebi.ac.uk/pdbsum/7prt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7prt ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[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;">
		+	== Publication Abstract from PubMed ==
		+	Heparan sulfate proteoglycans (HSPGs) mediate essential interactions throughout the extracellular matrix (ECM), providing signals that regulate cellular growth and development. Altered HSPG composition during tumorigenesis strongly aids cancer progression. Heparanase (HPSE) is the principal enzyme responsible for extracellular heparan sulfate catabolism and is markedly up-regulated in aggressive cancers. HPSE overactivity degrades HSPGs within the ECM, facilitating metastatic dissemination and releasing mitogens that drive cellular proliferation. Reducing extracellular HPSE activity reduces cancer growth, but few effective inhibitors are known, and none are clinically approved. Inspired by the natural glycosidase inhibitor cyclophellitol, we developed nanomolar mechanism-based, irreversible HPSE inhibitors that are effective within physiological environments. Application of cyclophellitol-derived HPSE inhibitors reduces cancer aggression in cellulo and significantly ameliorates murine metastasis. Mechanism-based irreversible HPSE inhibition is an unexplored anticancer strategy. We demonstrate the feasibility of such compounds to control pathological HPSE-driven malignancies.
		+
		+	Mechanism-based heparanase inhibitors reduce cancer metastasis in vivo.,de Boer C, Armstrong Z, Lit VAJ, Barash U, Ruijgrok G, Boyango I, Weitzenberg MM, Schroder SP, Sarris AJC, Meeuwenoord NJ, Bule P, Kayal Y, Ilan N, Codee JDC, Vlodavsky I, Overkleeft HS, Davies GJ, Wu L Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2203167119. doi:, 10.1073/pnas.2203167119. Epub 2022 Jul 26. PMID:35881786<ref>PMID:35881786</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7prt" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z~~-disk~~]]	+	[[Category: Armstrong Z]]
		+	[[Category: Davies GJ]]
		+	[[Category: Wu L]]

OCA at 04:51, 3 August 2022

OCA — Wed, 03 Aug 2022 04:51:29 GMT

←Older revision		Revision as of 04:51, 3 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7prt ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7prt' size='340' side='right'caption='[[7prt]]' scene=''>
-	~~Authors~~: ~~Wu, L~~.~~, Armstrong, Z~~.~~, Davies, G~~.J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: Crystal~~ structure ~~of human heparanase in complex with covalent inhibitor CB678~~	+	</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=7prt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7prt OCA], [https://pdbe.org/7prt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7prt RCSB], [https://www.ebi.ac.uk/pdbsum/7prt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7prt ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: Wu, L]]	+	__TOC__
-	[[Category: ~~Davies, G.J~~]]	+	</StructureSection>
-	[[Category: ~~Armstrong,~~ Z]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 12:38, 3 November 2021

OCA — Wed, 03 Nov 2021 12:38:51 GMT

←Older revision		Revision as of 12:38, 3 November 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7prt is ON HOLD	+	The entry 7prt is ON HOLD until Paper Publication

	Authors: Wu, L., Armstrong, Z., Davies, G.J.		Authors: Wu, L., Armstrong, Z., Davies, G.J.

OCA: Protected "7prt" [edit=sysop:move=sysop]

OCA — Wed, 29 Sep 2021 07:40:20 GMT

Protected "7prt" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:40, 29 September 2021

OCA: New page: '''Unreleased structure''' The entry 7prt is ON HOLD Authors: Wu, L., Armstrong, Z., Davies, G.J. Description: Crystal structure of human heparanase in complex with covalent inhibitor ...

OCA — Wed, 29 Sep 2021 07:40:20 GMT

New page: '''Unreleased structure''' The entry 7prt is ON HOLD Authors: Wu, L., Armstrong, Z., Davies, G.J. Description: Crystal structure of human heparanase in complex with covalent inhibitor ...

New page

'''Unreleased structure'''

The entry 7prt is ON HOLD

Authors: Wu, L., Armstrong, Z., Davies, G.J.

Description: Crystal structure of human heparanase in complex with covalent inhibitor CB678
[[Category: Unreleased Structures]]
[[Category: Wu, L]]
[[Category: Davies, G.J]]
[[Category: Armstrong, Z]]