6d3y - Revision history

OCA at 15:17, 4 October 2023

2023-10-04T15:17:34Z

←Older revision		Revision as of 15:17, 4 October 2023
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	<StructureSection load='6d3y' size='340' side='right'caption='[[6d3y]], [[Resolution\|resolution]] 1.32Å' scene=''>		<StructureSection load='6d3y' size='340' side='right'caption='[[6d3y]], [[Resolution\|resolution]] 1.32Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d3y]] 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=6D3Y OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6D3Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d3y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Helianthus_annuus Helianthus annuus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D3Y FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=GOL:GLYCEROL'>GOL</scene~~>, ~~<scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.32Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>PLG ([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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/Plasmin Plasmin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.7 3.4.21.7]~~ </~~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=6d3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3y OCA], [https://pdbe.org/6d3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d3y RCSB], [https://www.ebi.ac.uk/pdbsum/6d3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3y 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=6d3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3y OCA], [~~http~~://pdbe.org/6d3y PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6d3y RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6d3y PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3y ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN]] Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:[~~http~~://omim.org/entry/217090 217090]]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.<ref>PMID:1986355</ref> <ref>PMID:8392398</ref> <ref>PMID:6216475</ref> <ref>PMID:6238949</ref> <ref>PMID:1427790</ref> <ref>PMID:9242524</ref> <ref>PMID:9858247</ref> <ref>PMID:10233898</ref>	+	[https://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN] Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:[https://omim.org/entry/217090 217090]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.<ref>PMID:1986355</ref> <ref>PMID:8392398</ref> <ref>PMID:6216475</ref> <ref>PMID:6238949</ref> <ref>PMID:1427790</ref> <ref>PMID:9242524</ref> <ref>PMID:9858247</ref> <ref>PMID:10233898</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN]] Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.<ref>PMID:14699093</ref> Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.<ref>PMID:14699093</ref> ~~[[http://www.uniprot.org/uniprot/SFTI1_HELAN SFTI1_HELAN]] Inhibits trypsin, cathepsin G, elastase, chymotrypsin and thrombin. Does not inhibit factor Xa.<ref>PMID:10390350</ref>~~	+	[https://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN] Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.<ref>PMID:14699093</ref> Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.<ref>PMID:14699093</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6d3y" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6d3y" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Plasminogen 3D structures\|Plasminogen 3D structures]]
		+	*[[Trypsin inhibitor 3D structures\|Trypsin inhibitor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Helianthus annuus]]
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Plasmin]]~~	+	[[Category: Law RHP]]
-	[[Category: Law~~, R H.P~~]]	+	[[Category: Wu G]]
-	[[Category: Wu, G]]	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Fibrinolysis]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Sfti~~]]	+

OCA at 09:06, 1 May 2019

2019-05-01T09:06:47Z

←Older revision		Revision as of 09:06, 1 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6d3y is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Highly Potent and Selective Plasmin Inhibitors Based on the Sunflower Trypsin Inhibitor-1 Scaffold Attenuate Fibrinolysis in Plasma==
		+	<StructureSection load='6d3y' size='340' side='right'caption='[[6d3y]], [[Resolution\|resolution]] 1.32Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6d3y]] 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=6D3Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3Y FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PLG ([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/Plasmin Plasmin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.7 3.4.21.7] </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=6d3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3y OCA], [http://pdbe.org/6d3y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3y RCSB], [http://www.ebi.ac.uk/pdbsum/6d3y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3y ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN]] Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:[http://omim.org/entry/217090 217090]]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.<ref>PMID:1986355</ref> <ref>PMID:8392398</ref> <ref>PMID:6216475</ref> <ref>PMID:6238949</ref> <ref>PMID:1427790</ref> <ref>PMID:9242524</ref> <ref>PMID:9858247</ref> <ref>PMID:10233898</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN]] Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.<ref>PMID:14699093</ref> Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.<ref>PMID:14699093</ref> [[http://www.uniprot.org/uniprot/SFTI1_HELAN SFTI1_HELAN]] Inhibits trypsin, cathepsin G, elastase, chymotrypsin and thrombin. Does not inhibit factor Xa.<ref>PMID:10390350</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Antifibrinolytic drugs provide important pharmacological interventions to reduce morbidity and mortality from excessive bleeding during surgery and after trauma. Current drugs used for inhibiting the dissolution of fibrin, the main structural component of blood clots, are associated with adverse events due to lack of potency, high doses, and nonselective inhibition mechanisms. These drawbacks warrant the development of a new generation of highly potent and selective fibrinolysis inhibitors. Here, we use the 14-amino acid backbone-cyclic sunflower trypsin inhibitor-1 scaffold to design a highly potent ( Ki = 0.05 nM) inhibitor of the primary serine protease in fibrinolysis, plasmin. This compound displays a million-fold selectivity over other serine proteases in blood, inhibits fibrinolysis in plasma more effectively than the gold-standard therapeutic inhibitor aprotinin, and is a promising candidate for development of highly specific fibrinolysis inhibitors with reduced side effects.

-	~~Authors~~:	+	Highly Potent and Selective Plasmin Inhibitors Based on the Sunflower Trypsin Inhibitor-1 Scaffold Attenuate Fibrinolysis in Plasma.,Swedberg JE, Wu G, Mahatmanto T, Durek T, Caradoc-Davies TT, Whisstock JC, Law RHP, Craik DJ J Med Chem. 2019 Jan 24;62(2):552-560. doi: 10.1021/acs.jmedchem.8b01139. Epub, 2018 Dec 26. PMID:30520638<ref>PMID:30520638</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6d3y" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Plasmin]]
		+	[[Category: Law, R H.P]]
		+	[[Category: Wu, G]]
		+	[[Category: Complex]]
		+	[[Category: Fibrinolysis]]
		+	[[Category: Hydrolase]]
		+	[[Category: Protease]]
		+	[[Category: Sfti]]

OCA at 04:01, 30 May 2018

2018-05-30T04:01:06Z

←Older revision		Revision as of 04:01, 30 May 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6d3y is ON HOLD	+	The entry 6d3y is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6d3y" [edit=sysop:move=sysop]

2018-04-25T04:10:23Z

Protected "6d3y" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:10, 25 April 2018

OCA: New page: '''Unreleased structure''' The entry 6d3y is ON HOLD Authors: Description: Category: Unreleased Structures

2018-04-25T04:10:22Z

New page: '''Unreleased structure''' The entry 6d3y is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6d3y is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]