7lcu - Revision history

OCA at 15:43, 18 October 2023

2023-10-18T15:43:44Z

←Older revision		Revision as of 15:43, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7lcu]] 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=7LCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCU FirstGlance]. <br>		<table><tr><td colspan='2'>[[7lcu]] 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=7LCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XTA:(1-{[2-(3,5-dichlorophenyl)-6-{[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]oxy}pyridin-4-yl]methyl}piperidin-4-yl)acetic+acid'>XTA</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]] 1.24Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XTA:(1-{[2-(3,5-dichlorophenyl)-6-{[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]oxy}pyridin-4-yl]methyl}piperidin-4-yl)acetic+acid'>XTA</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=7lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lcu OCA], [https://pdbe.org/7lcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lcu RCSB], [https://www.ebi.ac.uk/pdbsum/7lcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lcu 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=7lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lcu OCA], [https://pdbe.org/7lcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lcu RCSB], [https://www.ebi.ac.uk/pdbsum/7lcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lcu ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/FURIN_HUMAN FURIN_HUMAN]] Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.<ref>PMID:7690548</ref>	+	[https://www.uniprot.org/uniprot/FURIN_HUMAN FURIN_HUMAN] Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.<ref>PMID:7690548</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 04:40, 8 September 2022

2022-09-08T04:40:10Z

←Older revision		Revision as of 04:40, 8 September 2022
Line 3:		Line 3:
	<StructureSection load='7lcu' size='340' side='right'caption='[[7lcu]], [[Resolution\|resolution]] 1.24Å' scene=''>		<StructureSection load='7lcu' size='340' side='right'caption='[[7lcu]], [[Resolution\|resolution]] 1.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7lcu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lcu]] 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=7LCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XTA:(1-{[2-(3,5-dichlorophenyl)-6-{[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]oxy}pyridin-4-yl]methyl}piperidin-4-yl)acetic+acid'>XTA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XTA:(1-{[2-(3,5-dichlorophenyl)-6-{[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]oxy}pyridin-4-yl]methyl}piperidin-4-yl)acetic+acid'>XTA</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Furin Furin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.75 3.4.21.75] </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=7lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lcu OCA], [https://pdbe.org/7lcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lcu RCSB], [https://www.ebi.ac.uk/pdbsum/7lcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lcu 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=7lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lcu OCA], [https://pdbe.org/7lcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lcu RCSB], [https://www.ebi.ac.uk/pdbsum/7lcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lcu ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/FURIN_HUMAN FURIN_HUMAN]] Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.<ref>PMID:7690548</ref>	+	[[https://www.uniprot.org/uniprot/FURIN_HUMAN FURIN_HUMAN]] Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.<ref>PMID:7690548</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Furin~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Campobasso, N]]	+	[[Category: Campobasso N]]
-	[[Category: Reid, R]]	+	[[Category: Reid R]]
-	~~[[Category: Hydrolase-inhibitor complex]]~~	+
-	~~[[Category: Inhibitor protease~~]]	+

OCA at 18:14, 27 July 2022

2022-07-27T18:14:11Z

←Older revision		Revision as of 18:14, 27 July 2022
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	==X-ray structure of Furin bound to BOS-318, a small molecule inhibitor==		==X-ray structure of Furin bound to BOS-318, a small molecule inhibitor==
-	<StructureSection load='7lcu' size='340' side='right'caption='[[7lcu]]' scene=''>	+	<StructureSection load='7lcu' size='340' side='right'caption='[[7lcu]], [[Resolution\|resolution]] 1.24Å' 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=7LCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lcu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCU 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=7lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lcu OCA], [https://pdbe.org/7lcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lcu RCSB], [https://www.ebi.ac.uk/pdbsum/7lcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lcu 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XTA:(1-{[2-(3,5-dichlorophenyl)-6-{[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]oxy}pyridin-4-yl]methyl}piperidin-4-yl)acetic+acid'>XTA</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Furin Furin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.75 3.4.21.75] </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=7lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lcu OCA], [https://pdbe.org/7lcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lcu RCSB], [https://www.ebi.ac.uk/pdbsum/7lcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lcu ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/FURIN_HUMAN FURIN_HUMAN]] Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.<ref>PMID:7690548</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In cystic fibrosis (CF), excessive furin activity plays a critical role in the activation of the epithelial sodium channel (ENaC), dysregulation of which contributes to airway dehydration, ineffective mucociliary clearance (MCC), and mucus obstruction. Here, we report a highly selective, cell-permeable furin inhibitor, BOS-318, that derives selectivity by eliciting the formation of a new, unexpected binding pocket independent of the active site catalytic triad. Using human ex vivo models, BOS-318 showed significant suppression of ENaC, which led to enhanced airway hydration and an approximately 30-fold increase in MCC rate. Furin inhibition also protected ENaC from subsequent activation by neutrophil elastase, a soluble protease dominant in CF airways. Additional therapeutic benefits include protection against epithelial cell death induced by Pseudomonas aeruginosa exotoxin A. Our findings demonstrate the utility of selective furin inhibition as a mutation-agnostic approach that can correct features of CF airway pathophysiology in a manner expected to deliver therapeutic value.
		+
		+	A highly selective, cell-permeable furin inhibitor BOS-318 rescues key features of cystic fibrosis airway disease.,Douglas LEJ, Reihill JA, Ho MWY, Axten JM, Campobasso N, Schneck JL, Rendina AR, Wilcoxen KM, Martin SL Cell Chem Biol. 2022 Jun 16;29(6):947-957.e8. doi:, 10.1016/j.chembiol.2022.02.001. Epub 2022 Feb 23. PMID:35202587<ref>PMID:35202587</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lcu" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Furin]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Campobasso N]]	+	[[Category: Campobasso, N]]
-	[[Category: Reid R]]	+	[[Category: Reid, R]]
		+	[[Category: Hydrolase-inhibitor complex]]
		+	[[Category: Inhibitor protease]]

OCA at 09:56, 12 January 2022

2022-01-12T09:56:57Z

←Older revision		Revision as of 09:56, 12 January 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7lcu ~~is ON HOLD until Paper Publication~~	+	==X-ray structure of Furin bound to BOS-318, a small molecule inhibitor==
-		+	<StructureSection load='7lcu' size='340' side='right'caption='[[7lcu]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCU FirstGlance]. <br>
-	~~Description~~:	+	</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=7lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lcu OCA], [https://pdbe.org/7lcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lcu RCSB], [https://www.ebi.ac.uk/pdbsum/7lcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lcu ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Campobasso N]]
		+	[[Category: Reid R]]

OCA at 09:15, 10 February 2021

2021-02-10T09:15:53Z

←Older revision		Revision as of 09:15, 10 February 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

2021-01-20T06:55:25Z

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

←Older revision

Revision as of 06:55, 20 January 2021

OCA: New page: '''Unreleased structure''' The entry 7lcu is ON HOLD Authors: Description: Category: Unreleased Structures

2021-01-20T06:55:24Z

New page: '''Unreleased structure''' The entry 7lcu is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7lcu is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]