7qy2 - Revision history

OCA at 13:23, 1 February 2024

OCA — Thu, 01 Feb 2024 13:23:51 GMT

←Older revision		Revision as of 13:23, 1 February 2024
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	<StructureSection load='7qy2' size='340' side='right'caption='[[7qy2]], [[Resolution\|resolution]] 1.55Å' scene=''>		<StructureSection load='7qy2' size='340' side='right'caption='[[7qy2]], [[Resolution\|resolution]] 1.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7qy2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QY2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7qy2]] 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=7QY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QY2 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=I0Q:(2R)-4-[4-[5-[4-[[4-(acetamidomethyl)piperidin-1-ium-1-yl]methyl]-6-[3,5-bis(chloranyl)phenyl]pyridin-2-yl]oxypyrimidin-2-yl]piperazin-1-ium-1-yl]-2-methyl-butanoate'>I0Q</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 1.55Å</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='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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=I0Q:(2R)-4-[4-[5-[4-[[4-(acetamidomethyl)piperidin-1-ium-1-yl]methyl]-6-[3,5-bis(chloranyl)phenyl]pyridin-2-yl]oxypyrimidin-2-yl]piperazin-1-ium-1-yl]-2-methyl-butanoate'>I0Q</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7qy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qy2 OCA], [https://pdbe.org/7qy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qy2 RCSB], [https://www.ebi.ac.uk/pdbsum/7qy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qy2 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=7qy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qy2 OCA], [https://pdbe.org/7qy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qy2 RCSB], [https://www.ebi.ac.uk/pdbsum/7qy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qy2 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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Furin~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brandstetter, H]]	+	[[Category: Brandstetter H]]
-	[[Category: Dahms~~, S O~~]]	+	[[Category: Dahms SO]]
-	[[Category: Pautsch, A]]	+	[[Category: Pautsch A]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Proprotein convertase]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Sars-cov-2~~]]	+

OCA at 11:52, 27 April 2022

OCA — Wed, 27 Apr 2022 11:52:42 GMT

←Older revision		Revision as of 11:52, 27 April 2022
Line 1:		Line 1:

	==X-ray structure of furin in complex with the dichlorophenylpyridine-based inhibitor 2==		==X-ray structure of furin in complex with the dichlorophenylpyridine-based inhibitor 2==
-	<StructureSection load='7qy2' size='340' side='right'caption='[[7qy2]]' scene=''>	+	<StructureSection load='7qy2' size='340' side='right'caption='[[7qy2]], [[Resolution\|resolution]] 1.55Å' 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=7QY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QY2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7qy2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QY2 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=7qy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qy2 OCA], [https://pdbe.org/7qy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qy2 RCSB], [https://www.ebi.ac.uk/pdbsum/7qy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qy2 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=I0Q:(2R)-4-[4-[5-[4-[[4-(acetamidomethyl)piperidin-1-ium-1-yl]methyl]-6-[3,5-bis(chloranyl)phenyl]pyridin-2-yl]oxypyrimidin-2-yl]piperazin-1-ium-1-yl]-2-methyl-butanoate'>I0Q</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7qy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qy2 OCA], [https://pdbe.org/7qy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qy2 RCSB], [https://www.ebi.ac.uk/pdbsum/7qy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qy2 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 ==
		+	Inhibitors of the proprotein convertase furin might serve as broad-spectrum antiviral therapeutics. High cellular potency and antiviral activity against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported for (3,5-dichlorophenyl)pyridine-derived furin inhibitors. Here we characterized the binding mechanism of this inhibitor class using structural, biophysical, and biochemical methods. We established a MALDI-TOF-MS-based furin activity assay, determined IC50 values, and solved X-ray structures of (3,5-dichlorophenyl)pyridine-derived compounds in complex with furin. The inhibitors induced a substantial conformational rearrangement of the active-site cleft by exposing a central buried tryptophan residue. These changes formed an extended hydrophobic surface patch where the 3,5-dichlorophenyl moiety of the inhibitors was inserted into a newly formed binding pocket. Consistent with these structural rearrangements, we observed slow off-rate binding kinetics and strong structural stabilization in surface plasmon resonance and differential scanning fluorimetry experiments, respectively. The discovered furin conformation offers new opportunities for structure-based drug discovery.
		+
		+	Dichlorophenylpyridine-Based Molecules Inhibit Furin through an Induced-Fit Mechanism.,Dahms SO, Schnapp G, Winter M, Buttner FH, Schleputz M, Gnamm C, Pautsch A, Brandstetter H ACS Chem Biol. 2022 Apr 15;17(4):816-821. doi: 10.1021/acschembio.2c00103. Epub, 2022 Apr 4. PMID:35377598<ref>PMID:35377598</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7qy2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Furin]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brandstetter H]]	+	[[Category: Brandstetter, H]]
-	[[Category: Dahms SO]]	+	[[Category: Dahms, S O]]
-	[[Category: Pautsch A]]	+	[[Category: Pautsch, A]]
		+	[[Category: Complex]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Proprotein convertase]]
		+	[[Category: Protease]]
		+	[[Category: Sars-cov-2]]

OCA at 02:55, 21 April 2022

OCA — Thu, 21 Apr 2022 02:55:48 GMT

←Older revision		Revision as of 02:55, 21 April 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7qy2 is ~~ON HOLD until Paper Publication~~	+	==X-ray structure of furin in complex with the dichlorophenylpyridine-based inhibitor 2==
-		+	<StructureSection load='7qy2' size='340' side='right'caption='[[7qy2]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QY2 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=7qy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qy2 OCA], [https://pdbe.org/7qy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qy2 RCSB], [https://www.ebi.ac.uk/pdbsum/7qy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qy2 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Brandstetter H]]
		+	[[Category: Dahms SO]]
		+	[[Category: Pautsch A]]

OCA at 06:25, 23 February 2022

OCA — Wed, 23 Feb 2022 06:25:31 GMT

←Older revision		Revision as of 06:25, 23 February 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7qy2 is ON HOLD	+	The entry 7qy2 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7qy2" [edit=sysop:move=sysop]

OCA — Wed, 02 Feb 2022 05:32:59 GMT

Protected "7qy2" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:32, 2 February 2022

OCA: New page: '''Unreleased structure''' The entry 7qy2 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 02 Feb 2022 05:32:57 GMT

New page: '''Unreleased structure''' The entry 7qy2 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7qy2 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]