7l7o - Revision history

OCA at 15:40, 18 October 2023

OCA — Wed, 18 Oct 2023 15:40:14 GMT

←Older revision		Revision as of 15:40, 18 October 2023
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	==Crystal structure of HCV NS3/4A D168A protease in complex with NR04-49==		==Crystal structure of HCV NS3/4A D168A protease in complex with NR04-49==
-	<StructureSection load='7l7o' size='340' side='right'caption='[[7l7o]]' scene=''>	+	<StructureSection load='7l7o' size='340' side='right'caption='[[7l7o]], [[Resolution\|resolution]] 1.72Å' 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=7L7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L7O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7l7o]] 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=7L7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L7O 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=7l7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7o OCA], [https://pdbe.org/7l7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7o RCSB], [https://www.ebi.ac.uk/pdbsum/7l7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7o ProSAT]</span></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]] 1.72Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XSY:(1R,3r,5S)-bicyclo[3.1.0]hexan-3-yl+[(2R,6S,12Z,13aS,14aR,16aS)-2-{[6-methoxy-3-(trifluoromethyl)quinoxalin-2-yl]oxy}-14a-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl]carbamate'>XSY</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=7l7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7o OCA], [https://pdbe.org/7l7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7o RCSB], [https://www.ebi.ac.uk/pdbsum/7l7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7o ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A8DG50_9HEPC A8DG50_9HEPC]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The three pan-genotypic HCV NS3/4A protease inhibitors (PIs) currently in clinical use-grazoprevir, glecaprevir, and voxilaprevir-are quinoxaline-based P2-P4 macrocycles and thus exhibit similar resistance profiles. Using our quinoxaline-based P1-P3 macrocyclic lead compounds as an alternative chemical scaffold, we explored structure-activity relationships (SARs) at the P2 and P4 positions to develop pan-genotypic PIs that avoid drug resistance. A structure-guided strategy was used to design and synthesize two series of compounds with different P2 quinoxalines in combination with diverse P4 groups of varying sizes and shapes, with and without fluorine substitutions. Our SAR data and cocrystal structures revealed the interplay between the P2 and P4 groups, which influenced inhibitor binding and the overall resistance profile. Optimizing inhibitor interactions in the S4 pocket led to PIs with excellent antiviral activity against clinically relevant PI-resistant HCV variants and genotype 3, providing potential pan-genotypic inhibitors with improved resistance profiles.
		+
		+	Discovery of Quinoxaline-Based P1-P3 Macrocyclic NS3/4A Protease Inhibitors with Potent Activity against Drug-Resistant Hepatitis C Virus Variants.,Nageswara Rao D, Zephyr J, Henes M, Chan ET, Matthew AN, Hedger AK, Conway HL, Saeed M, Newton A, Petropoulos CJ, Huang W, Kurt Yilmaz N, Schiffer CA, Ali A J Med Chem. 2021 Aug 26;64(16):11972-11989. doi: 10.1021/acs.jmedchem.1c00554., Epub 2021 Aug 18. PMID:34405680<ref>PMID:34405680</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7l7o" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hepacivirus C]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Schiffer CA]]		[[Category: Schiffer CA]]
	[[Category: Zephyr J]]		[[Category: Zephyr J]]

OCA at 09:05, 8 September 2021

OCA — Wed, 08 Sep 2021 09:05:13 GMT

←Older revision		Revision as of 09:05, 8 September 2021
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-	'''Unreleased structure'''

-	~~The entry 7l7o is ON HOLD until Paper Publication~~	+	==Crystal structure of HCV NS3/4A D168A protease in complex with NR04-49==
-		+	<StructureSection load='7l7o' size='340' side='right'caption='[[7l7o]]' scene=''>
-	~~Authors: Zephyr, J., Schiffer, C.A.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L7O FirstGlance]. <br>
-	~~Description:~~ Crystal structure of HCV NS3/4A D168A protease in complex with NR04-49	+	</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=7l7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7o OCA], [https://pdbe.org/7l7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7o RCSB], [https://www.ebi.ac.uk/pdbsum/7l7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7o ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Schiffer~~, C.A~~]]	+	__TOC__
-	[[Category: Zephyr, J]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Schiffer CA]]
		+	[[Category: Zephyr J]]

OCA at 05:36, 24 February 2021

OCA — Wed, 24 Feb 2021 05:36:24 GMT

←Older revision		Revision as of 05:36, 24 February 2021
Line 5:		Line 5:
	Authors: Zephyr, J., Schiffer, C.A.		Authors: Zephyr, J., Schiffer, C.A.

-	Description: Crystal structure of HCV NS3/4A D168A protease in complex with ~~NR01~~-~~129~~	+	Description: Crystal structure of HCV NS3/4A D168A protease in complex with NR04-49
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Zephyr, J]]
	[[Category: Schiffer, C.A]]		[[Category: Schiffer, C.A]]
		+	[[Category: Zephyr, J]]

OCA at 08:40, 17 February 2021

OCA — Wed, 17 Feb 2021 08:40:52 GMT

←Older revision		Revision as of 08:40, 17 February 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7l7o is ON HOLD	+	The entry 7l7o is ON HOLD until Paper Publication

	Authors: Zephyr, J., Schiffer, C.A.		Authors: Zephyr, J., Schiffer, C.A.

OCA: Protected "7l7o" [edit=sysop:move=sysop]

OCA — Wed, 06 Jan 2021 05:53:54 GMT

Protected "7l7o" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:53, 6 January 2021

OCA: New page: '''Unreleased structure''' The entry 7l7o is ON HOLD Authors: Zephyr, J., Schiffer, C.A. Description: Crystal structure of HCV NS3/4A D168A protease in complex with NR01-129 [[Category...

OCA — Wed, 06 Jan 2021 05:53:51 GMT

New page: '''Unreleased structure''' The entry 7l7o is ON HOLD Authors: Zephyr, J., Schiffer, C.A. Description: Crystal structure of HCV NS3/4A D168A protease in complex with NR01-129 [[Category...

New page

'''Unreleased structure'''

The entry 7l7o is ON HOLD

Authors: Zephyr, J., Schiffer, C.A.

Description: Crystal structure of HCV NS3/4A D168A protease in complex with NR01-129
[[Category: Unreleased Structures]]
[[Category: Zephyr, J]]
[[Category: Schiffer, C.A]]