6cvx - Revision history

OCA at 15:11, 4 October 2023

OCA — Wed, 04 Oct 2023 15:11:55 GMT

←Older revision		Revision as of 15:11, 4 October 2023
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	<StructureSection load='6cvx' size='340' side='right'caption='[[6cvx]], [[Resolution\|resolution]] 1.78Å' scene=''>		<StructureSection load='6cvx' size='340' side='right'caption='[[6cvx]], [[Resolution\|resolution]] 1.78Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cvx]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~9hepc 9hepc~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CVX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6CVX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cvx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CVX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FH4:N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2S)-2-ethenyl-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-4-{[7-methoxy-3-(propan-2-yl)quinoxalin-2-yl]oxy}-L-prolinamide'>FH4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.779Å</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=6cvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cvx OCA], [~~http~~://pdbe.org/6cvx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6cvx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6cvx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6cvx ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FH4:N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2S)-2-ethenyl-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-4-{[7-methoxy-3-(propan-2-yl)quinoxalin-2-yl]oxy}-L-prolinamide'>FH4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6cvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cvx OCA], [https://pdbe.org/6cvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cvx RCSB], [https://www.ebi.ac.uk/pdbsum/6cvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cvx ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A0B4WYC6_9HEPC A0A0B4WYC6_9HEPC]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 16:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6cvx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6cvx" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hepacivirus C]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Matthew~~, A N~~]]	+	[[Category: Matthew AN]]
-	[[Category: Schiffer~~, C A]]~~	+	[[Category: Schiffer CA]]
-	~~[[Category: Drug resistance]]~~	+
-	~~[[Category: Hepatitis c virus]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Ns3/4a protease]]~~	+
-	~~[[Category: Protease inhibitor~~]]	+

OCA at 09:52, 18 December 2019

OCA — Wed, 18 Dec 2019 09:52:31 GMT

←Older revision		Revision as of 09:52, 18 December 2019
Line 1:		Line 1:

	==Crystal structure of HCV NS3/4A WT protease in complex with AJ-50 (MK-5172 linear analogue)==		==Crystal structure of HCV NS3/4A WT protease in complex with AJ-50 (MK-5172 linear analogue)==
-	<StructureSection load='6cvx' size='340' side='right' caption='[[6cvx]], [[Resolution\|resolution]] 1.78Å' scene=''>	+	<StructureSection load='6cvx' size='340' side='right'caption='[[6cvx]], [[Resolution\|resolution]] 1.78Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cvx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CVX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cvx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CVX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FH4:N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2S)-2-ethenyl-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-4-{[7-methoxy-3-(propan-2-yl)quinoxalin-2-yl]oxy}-L-prolinamide'>FH4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FH4:N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2S)-2-ethenyl-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-4-{[7-methoxy-3-(propan-2-yl)quinoxalin-2-yl]oxy}-L-prolinamide'>FH4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6cvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cvx OCA], [http://pdbe.org/6cvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cvx RCSB], [http://www.ebi.ac.uk/pdbsum/6cvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cvx 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=6cvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cvx OCA], [http://pdbe.org/6cvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cvx RCSB], [http://www.ebi.ac.uk/pdbsum/6cvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cvx ProSAT]</span></td></tr>
Line 20:		Line 20:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Matthew, A N]]		[[Category: Matthew, A N]]
	[[Category: Schiffer, C A]]		[[Category: Schiffer, C A]]

OCA at 21:47, 9 August 2018

OCA — Thu, 09 Aug 2018 21:47:35 GMT

←Older revision		Revision as of 21:47, 9 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6cvx is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of HCV NS3/4A WT protease in complex with AJ-50 (MK-5172 linear analogue)==
		+	<StructureSection load='6cvx' size='340' side='right' caption='[[6cvx]], [[Resolution\|resolution]] 1.78Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6cvx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CVX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FH4:N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2S)-2-ethenyl-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-4-{[7-methoxy-3-(propan-2-yl)quinoxalin-2-yl]oxy}-L-prolinamide'>FH4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6cvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cvx OCA], [http://pdbe.org/6cvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cvx RCSB], [http://www.ebi.ac.uk/pdbsum/6cvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cvx ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A series of linear HCV NS3/4A protease inhibitors was designed by eliminating the P2-P4 macrocyclic linker in grazoprevir, which, in addition to conferring conformational flexibility, allowed structure-activity relationship (SAR) exploration of diverse quinoxalines at the P2 position. Biochemical and replicon data indicated preference for small hydrophobic groups at the 3-position of P2 quinoxaline for maintaining potency against resistant variants R155K, A156T, and D168A/V. The linear inhibitors, though generally less potent than the corresponding macrocyclic analogues, were relatively easier to synthesize and less susceptible to drug resistance. Three inhibitor cocrystal structures bound to wild-type NS3/4A protease revealed a conformation with subtle changes in the binding of P2 quinoxaline, depending on the 3-position substituent, likely impacting both inhibitor potency and resistance profile. The SAR and structural analysis highlight inhibitor features that strengthen interactions of the P2 moiety with the catalytic triad residues, providing valuable insights to improve potency against resistant variants.

-	~~Authors:~~ Matthew, A.N., Schiffer, C.A.	+	Quinoxaline-Based Linear HCV NS3/4A Protease Inhibitors Exhibit Potent Activity against Drug Resistant Variants.,Rusere LN, Matthew AN, Lockbaum GJ, Jahangir M, Newton A, Petropoulos CJ, Huang W, Kurt Yilmaz N, Schiffer CA, Ali A ACS Med Chem Lett. 2018 May 17;9(7):691-696. doi: 10.1021/acsmedchemlett.8b00150., eCollection 2018 Jul 12. PMID:30034602<ref>PMID:30034602</ref>

-	~~Description: Crystal structure~~ of ~~HCV NS3~~/~~4A WT protease in complex with AJ~~-~~50 (MK~~-~~5172 linear analogue)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Schiffer, C.A]]	+	<div class="pdbe-citations 6cvx" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Matthew, A.N~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Matthew, A N]]
		+	[[Category: Schiffer, C A]]
		+	[[Category: Drug resistance]]
		+	[[Category: Hepatitis c virus]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Ns3/4a protease]]
		+	[[Category: Protease inhibitor]]

OCA at 06:38, 2 May 2018

OCA — Wed, 02 May 2018 06:38:56 GMT

←Older revision		Revision as of 06:38, 2 May 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Matthew, A.N., Schiffer, C.A.		Authors: Matthew, A.N., Schiffer, C.A.

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

OCA — Wed, 11 Apr 2018 12:27:26 GMT

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

←Older revision

Revision as of 12:27, 11 April 2018

OCA: New page: '''Unreleased structure''' The entry 6cvx is ON HOLD Authors: Matthew, A.N., Schiffer, C.A. Description: Crystal structure of HCV NS3/4A WT protease in complex with AJ-50 (MK-5172 line...

OCA — Wed, 11 Apr 2018 12:27:24 GMT

New page: '''Unreleased structure''' The entry 6cvx is ON HOLD Authors: Matthew, A.N., Schiffer, C.A. Description: Crystal structure of HCV NS3/4A WT protease in complex with AJ-50 (MK-5172 line...

New page

'''Unreleased structure'''

The entry 6cvx is ON HOLD

Authors: Matthew, A.N., Schiffer, C.A.

Description: Crystal structure of HCV NS3/4A WT protease in complex with AJ-50 (MK-5172 linear analogue)
[[Category: Unreleased Structures]]
[[Category: Schiffer, C.A]]
[[Category: Matthew, A.N]]