5ugg - Revision history

OCA at 07:39, 17 October 2024

2024-10-17T07:39:48Z

← Older revision		Revision as of 07:39, 17 October 2024
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	<StructureSection load='5ugg' size='340' side='right'caption='[[5ugg]], [[Resolution\|resolution]] 1.20Å' scene=''>		<StructureSection load='5ugg' size='340' side='right'caption='[[5ugg]], [[Resolution\|resolution]] 1.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5ugg]] 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=5UGG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5UGG FirstGlance]. <br>		<table><tr><td colspan='2'>[[5ugg]] 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=5UGG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UGG FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=89M:Nalpha-[trans-4-(aminomethyl)cyclohexane-1-carbonyl]-N-octyl-O-[(quinolin-2-yl)methyl]-L-tyrosinamide'>89M</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]] 1.2Å</td></tr>
	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Related_structure~~\|~~Related:]]</b></td><td class="sblockDat">[[5ugd\|5ugd~~]]</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=89M:Nalpha-[trans-4-(aminomethyl)cyclohexane-1-carbonyl]-N-octyl-O-[(quinolin-2-yl)methyl]-L-tyrosinamide'>89M</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ugg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ugg OCA], [https://pdbe.org/5ugg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ugg RCSB], [https://www.ebi.ac.uk/pdbsum/5ugg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ugg ProSAT]</span></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=5ugg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ugg OCA], [~~http~~://pdbe.org/5ugg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ugg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ugg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ugg 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>		[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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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Plasmin]]~~		[[Category: Law RHP]]
	[[Category: Law~~, R H.P~~]]		[[Category: Whisstock JC]]
	[[Category: Whisstock~~, J C~~]]		[[Category: Wu G]]
	[[Category: Wu, G]]
	~~[[Category: Fibrinolysis]]~~
	~~[[Category: Hydrolase-inhibitor complex]]~~
	~~[[Category: Inhibitor]]~~
	~~[[Category: Yo~~]]

OCA at 08:22, 8 January 2020

2020-01-08T08:22:36Z

← Older revision		Revision as of 08:22, 8 January 2020
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	==Protease Inhibitor==		==Protease Inhibitor==
	<StructureSection load='5ugg' size='340' side='right' caption='[[5ugg]], [[Resolution\|resolution]] 1.20Å' scene=''>		<StructureSection load='5ugg' size='340' side='right'caption='[[5ugg]], [[Resolution\|resolution]] 1.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5ugg]] 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=5UGG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UGG FirstGlance]. <br>		<table><tr><td colspan='2'>[[5ugg]] 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=5UGG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UGG FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 5ugg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ugg" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Plasminogen 3D structures\|Plasminogen 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Plasmin]]		[[Category: Plasmin]]
	[[Category: Law, R H.P]]		[[Category: Law, R H.P]]

OCA at 08:13, 17 January 2018

2018-01-17T08:13:58Z

← Older revision		Revision as of 08:13, 17 January 2018
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	== 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/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;">
			== Publication Abstract from PubMed ==
			The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, and bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results in life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors of this system are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents plasminogen activation through blocking recruitment to target substrates, is the most widely used inhibitor for the plasminogen/plasmin system in therapeutics. However, TXA lacks efficacy on the active form of plasmin. Thus, there is a need to develop specific inhibitors that target the protease active site. Here we report the crystal structures of plasmin in complex with the novel YO (trans-4-aminomethylcyclohexanecarbonyl-l-tyrosine-n-octylamide) class of small molecule inhibitors. We found that these inhibitors form key interactions with the S1 and S3' subsites of the catalytic cleft. Here, the TXA moiety of the YO compounds inserts into the primary (S1) specificity pocket, suggesting that TXA itself may function as a weak plasmin inhibitor, a hypothesis supported by subsequent biochemical and biophysical analyses. Mutational studies reveal that F587 of the S' subsite plays a key role in mediating the inhibitor interaction. Taken together, these data provide a foundation for the future development of small molecule inhibitors to specifically regulate plasmin function in a range of diseases and disorders.

			X-ray crystal structure of plasmin with tranexamic acid-derived active site inhibitors.,Law RHP, Wu G, Leung EWW, Hidaka K, Quek AJ, Caradoc-Davies TT, Jeevarajah D, Conroy PJ, Kirby NM, Norton RS, Tsuda Y, Whisstock JC Blood Adv. 2017 May 9;1(12):766-771. doi: 10.1182/bloodadvances.2016004150., eCollection 2017 May 9. PMID:29296720<ref>PMID:29296720</ref>

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

OCA at 14:33, 6 November 2017

2017-11-06T14:33:44Z

← Older revision		Revision as of 14:33, 6 November 2017
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	~~'''Unreleased structure'''~~

	~~The entry~~ 5ugg is ~~ON HOLD until Paper Publication~~		==Protease Inhibitor==
			<StructureSection load='5ugg' size='340' side='right' caption='[[5ugg]], [[Resolution\|resolution]] 1.20Å' scene=''>
	~~Authors~~: ~~Law~~, R.H.P., Wu, G., ~~Whisstock~~, J.C.		== Structural highlights ==
			<table><tr><td colspan='2'>[[5ugg]] 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=5UGG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UGG FirstGlance]. <br>
	~~Description~~: ~~Protease Inhibitor~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=89M:Nalpha-[trans-4-(aminomethyl)cyclohexane-1-carbonyl]-N-octyl-O-[(quinolin-2-yl)methyl]-L-tyrosinamide'>89M</scene></td></tr>
	[[Category: ~~Unreleased Structures~~]]		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ugd\|5ugd]]</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=5ugg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ugg OCA], [http://pdbe.org/5ugg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ugg RCSB], [http://www.ebi.ac.uk/pdbsum/5ugg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ugg 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>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Human]]
			[[Category: Plasmin]]
			[[Category: Law, R H.P]]
			[[Category: Whisstock, J C]]
	[[Category: Wu, G]]		[[Category: Wu, G]]
	[[Category: ~~Law, R.H.P~~]]		[[Category: Fibrinolysis]]
	[[Category: ~~Whisstock, J.C~~]]		[[Category: Hydrolase-inhibitor complex]]
			[[Category: Inhibitor]]
			[[Category: Yo]]

OCA at 11:05, 5 April 2017

2017-04-05T11:05:22Z

← Older revision		Revision as of 11:05, 5 April 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5ugg is ON HOLD		The entry 5ugg is ON HOLD until Paper Publication

	Authors: Law, R.H.P., Wu, G., Whisstock, J.C.		Authors: Law, R.H.P., Wu, G., Whisstock, J.C.

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

2017-01-18T14:57:29Z

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

← Older revision	Revision as of 14:57, 18 January 2017
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5ugg is ON HOLD Authors: Law, R.H.P., Wu, G., Whisstock, J.C. Description: Protease Inhibitor Category: Unreleased Structures [[Category: Wu, G...

2017-01-18T14:57:27Z

New page: '''Unreleased structure''' The entry 5ugg is ON HOLD Authors: Law, R.H.P., Wu, G., Whisstock, J.C. Description: Protease Inhibitor Category: Unreleased Structures [[Category: Wu, G...

New page

'''Unreleased structure'''

The entry 5ugg is ON HOLD

Authors: Law, R.H.P., Wu, G., Whisstock, J.C.

Description: Protease Inhibitor
[[Category: Unreleased Structures]]
[[Category: Wu, G]]
[[Category: Law, R.H.P]]
[[Category: Whisstock, J.C]]