5zaj - Revision history

OCA at 08:50, 22 November 2023

2023-11-22T08:50:52Z

←Older revision		Revision as of 08:50, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='5zaj' size='340' side='right'caption='[[5zaj]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='5zaj' size='340' side='right'caption='[[5zaj]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zaj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZAJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5ZAJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zaj]] 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=5ZAJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZAJ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=32I:3-azanyl-5-(azepan~~-1~~-yl)-N-carbamimidoyl-6-(2,4-dimethoxypyrimidin-5-yl)pyrazine-2-carboxamide'>32I</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]] 1.65Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks'>[http~~:~~//en.wikipedia.org/wiki/U~~-~~plasminogen_activator U~~-~~plasminogen activator]~~, ~~with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73]~~ </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=32I:3-azanyl-5-(azepan-1-yl)-N-carbamimidoyl-6-(2,4-dimethoxypyrimidin-5-yl)pyrazine-2-carboxamide'>32I</scene></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=5zaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zaj OCA], [~~http~~://pdbe.org/5zaj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5zaj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5zaj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5zaj 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=5zaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zaj OCA], [https://pdbe.org/5zaj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zaj RCSB], [https://www.ebi.ac.uk/pdbsum/5zaj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zaj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[~~http~~://omim.org/entry/601709 601709]]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>	+	[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[https://omim.org/entry/601709 601709]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.	+	[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
	<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 5zaj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5zaj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Urokinase 3D Structures\|Urokinase 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: U-plasminogen activator]]~~	+	[[Category: Buckley BJ]]
-	[[Category: Buckley~~, B J~~]]	+	[[Category: Huang MD]]
-	[[Category: Huang~~, M D~~]]	+	[[Category: Jiang LG]]
-	[[Category: Jiang~~, L G~~]]	+	[[Category: Kelso MJ]]
-	[[Category: Kelso~~, M J~~]]	+	[[Category: Ranson M]]
-	[[Category: Ranson, M]]	+
-	~~[[Category: Amiloride]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Urokinase~~]]	+

OCA at 21:17, 28 October 2020

2020-10-28T21:17:33Z

←Older revision		Revision as of 21:17, 28 October 2020
Line 1:		Line 1:

	==uPA-31F==		==uPA-31F==
-	<StructureSection load='5zaj' size='340' side='right' caption='[[5zaj]], [[Resolution\|resolution]] 1.65Å' scene=''>	+	<StructureSection load='5zaj' size='340' side='right'caption='[[5zaj]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zaj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZAJ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ZAJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zaj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZAJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ZAJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=32I:3-azanyl-5-(azepan-1-yl)-N-carbamimidoyl-6-(2,4-dimethoxypyrimidin-5-yl)pyrazine-2-carboxamide'>32I</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=32I:3-azanyl-5-(azepan-1-yl)-N-carbamimidoyl-6-(2,4-dimethoxypyrimidin-5-yl)pyrazine-2-carboxamide'>32I</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </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=5zaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zaj OCA], [http://pdbe.org/5zaj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zaj RCSB], [http://www.ebi.ac.uk/pdbsum/5zaj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zaj 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=5zaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zaj OCA], [http://pdbe.org/5zaj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zaj RCSB], [http://www.ebi.ac.uk/pdbsum/5zaj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zaj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 25:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: U-plasminogen activator]]		[[Category: U-plasminogen activator]]
	[[Category: Buckley, B J]]		[[Category: Buckley, B J]]

OCA at 08:11, 19 December 2018

2018-12-19T08:11:16Z

←Older revision		Revision as of 08:11, 19 December 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5zaj is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==uPA-31F==
		+	<StructureSection load='5zaj' size='340' side='right' caption='[[5zaj]], [[Resolution\|resolution]] 1.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5zaj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZAJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZAJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=32I:3-azanyl-5-(azepan-1-yl)-N-carbamimidoyl-6-(2,4-dimethoxypyrimidin-5-yl)pyrazine-2-carboxamide'>32I</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </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=5zaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zaj OCA], [http://pdbe.org/5zaj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zaj RCSB], [http://www.ebi.ac.uk/pdbsum/5zaj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zaj ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[http://omim.org/entry/601709 601709]]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Metastasis is the cause of death in the majority ( approximately 90%) of malignant cancers. The oral potassium-sparing diuretic amiloride and its 5-substituted derivative 5 -N, N-(hexamethylene)amiloride (HMA) reportedly show robust antitumor/metastasis effects in multiple in vitro and animal models. These effects are likely due, at least in part, to inhibition of the urokinase plasminogen activator (uPA), a key protease determinant of cell invasiveness and metastasis. This study reports the discovery of 6-substituted HMA analogs that show nanomolar potency against uPA, high selectivity over related trypsin-like serine proteases, and minimal inhibitory effects against epithelial sodium channels (ENaC), the diuretic and antikaliuretic target of amiloride. Reductions in lung metastases were demonstrated for two analogs in a late-stage experimental mouse metastasis model, and one analog completely inhibited formation of liver metastases in an orthotopic xenograft mouse model of pancreatic cancer. The results support further evaluation of 6-substituted HMA derivatives as uPA-targeting anticancer drugs.

-	~~Authors:~~ Buckley, B., Jiang, ~~L.G.~~, ~~Huang~~, ~~M.D.~~, ~~Kelso~~, M., ~~Ranson~~, M.	+	6-Substituted Hexamethylene Amiloride (HMA) Derivatives as Potent and Selective Inhibitors of the Human Urokinase Plasminogen Activator for Use in Cancer.,Buckley BJ, Aboelela A, Minaei E, Jiang LX, Xu Z, Ali U, Fildes K, Cheung CY, Cook SM, Johnson DC, Bachovchin DA, Cook GM, Apte M, Huang M, Ranson M, Kelso MJ J Med Chem. 2018 Sep 27;61(18):8299-8320. doi: 10.1021/acs.jmedchem.8b00838. Epub, 2018 Sep 7. PMID:30130401<ref>PMID:30130401</ref>

-	~~Description~~: ~~uPA~~-~~31F~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5zaj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: U-plasminogen activator]]
		+	[[Category: Buckley, B J]]
		+	[[Category: Huang, M D]]
		+	[[Category: Jiang, L G]]
		+	[[Category: Kelso, M J]]
	[[Category: Ranson, M]]		[[Category: Ranson, M]]
-	[[Category: ~~Kelso, M~~]]	+	[[Category: Amiloride]]
-	[[Category: ~~Huang, M.D~~]]	+	[[Category: Hydrolase]]
-	[[Category: ~~Buckley, B]]~~	+	[[Category: Urokinase]]
-	~~[[Category: Jiang, L.G~~]]	+

OCA at 04:01, 18 April 2018

2018-04-18T04:01:42Z

←Older revision		Revision as of 04:01, 18 April 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

-	Authors: Buckley, B., Jiang, L.G., Huang, M.D., Kelso, K., Ranson, M.	+	Authors: Buckley, B., Jiang, L.G., Huang, M.D., Kelso, M., Ranson, M.

	Description: uPA-31F		Description: uPA-31F
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Ranson, M]]		[[Category: Ranson, M]]
-	[[Category: Kelso, K]]	+	[[Category: Kelso, M]]
	[[Category: Huang, M.D]]		[[Category: Huang, M.D]]
	[[Category: Buckley, B]]		[[Category: Buckley, B]]
	[[Category: Jiang, L.G]]		[[Category: Jiang, L.G]]

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

2018-02-15T05:12:10Z

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

←Older revision

Revision as of 05:12, 15 February 2018

OCA: New page: '''Unreleased structure''' The entry 5zaj is ON HOLD Authors: Buckley, B., Jiang, L.G., Huang, M.D., Kelso, K., Ranson, M. Description: uPA-31F Category: Unreleased Structures [[Ca...

2018-02-15T05:12:09Z

New page: '''Unreleased structure''' The entry 5zaj is ON HOLD Authors: Buckley, B., Jiang, L.G., Huang, M.D., Kelso, K., Ranson, M. Description: uPA-31F Category: Unreleased Structures [[Ca...

New page

'''Unreleased structure'''

The entry 5zaj is ON HOLD

Authors: Buckley, B., Jiang, L.G., Huang, M.D., Kelso, K., Ranson, M.

Description: uPA-31F
[[Category: Unreleased Structures]]
[[Category: Ranson, M]]
[[Category: Kelso, K]]
[[Category: Huang, M.D]]
[[Category: Buckley, B]]
[[Category: Jiang, L.G]]