7pfy - Revision history

OCA at 13:05, 1 February 2024

2024-02-01T13:05:03Z

←Older revision		Revision as of 13:05, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7pfy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Zika_virus Zika virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PFY FirstGlance]. <br>		<table><tr><td colspan='2'>[[7pfy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Zika_virus Zika virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PFY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAL:BETA-ALANINE'>BAL</scene>, <scene name='pdbligand=V7T:(2R)-6-azanyl-2-carbamimidamido-hexanoic+acid'>V7T</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]] 1.38Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAL:BETA-ALANINE'>BAL</scene>, <scene name='pdbligand=V7T:(2R)-6-azanyl-2-carbamimidamido-hexanoic+acid'>V7T</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=7pfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pfy OCA], [https://pdbe.org/7pfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pfy RCSB], [https://www.ebi.ac.uk/pdbsum/7pfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pfy 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=7pfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pfy OCA], [https://pdbe.org/7pfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pfy RCSB], [https://www.ebi.ac.uk/pdbsum/7pfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pfy ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:08, 21 December 2022

2022-12-21T10:08:09Z

←Older revision		Revision as of 10:08, 21 December 2022
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	==Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus in Complex with Inhibitor MI-2241==		==Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus in Complex with Inhibitor MI-2241==
-	<StructureSection load='7pfy' size='340' side='right'caption='[[7pfy]]' scene=''>	+	<StructureSection load='7pfy' size='340' side='right'caption='[[7pfy]], [[Resolution\|resolution]] 1.38Å' 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=7PFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PFY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7pfy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Zika_virus Zika virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PFY 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=7pfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pfy OCA], [https://pdbe.org/7pfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pfy RCSB], [https://www.ebi.ac.uk/pdbsum/7pfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pfy 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=BAL:BETA-ALANINE'>BAL</scene>, <scene name='pdbligand=V7T:(2R)-6-azanyl-2-carbamimidamido-hexanoic+acid'>V7T</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=7pfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pfy OCA], [https://pdbe.org/7pfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pfy RCSB], [https://www.ebi.ac.uk/pdbsum/7pfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pfy ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POLG_ZIKV POLG_ZIKV] Protein C: Encapsulates the genomic RNA.[UniProtKB:P17763] prM: Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated.[UniProtKB:P17763] Envelope protein E: Binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes.[UniProtKB:P17763] Non-structural protein 1: Involved in virus replication and regulation of the innate immune response.[UniProtKB:P17763] Non-structural protein 2A: May be involved viral RNA replication and capsid assembly.[UniProtKB:P09732] Non-structural protein 4A: Induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the helicase region of Serine protease NS3 chain.[UniProtKB:P17763] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[UniProtKB:P17763] Non-structural protein 4B: Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway.[UniProtKB:P17763]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Zika virus (ZIKV) is a human pathogenic arbovirus. So far, neither a specific treatment nor a vaccination against ZIKV infections has been approved. Starting from our previously described lead structure, a series of 29 new macrocyclic inhibitors of the Zika virus protease containing different linker motifs have been synthesized. By selecting hydrophobic d-amino acids as part of the linker, numerous inhibitors with K(i) values < 5 nM were obtained. For 12 inhibitors, crystal structures in complex with the ZIKV protease up to 1.30 A resolution were determined, which contribute to the understanding of the observed structure-activity relationship (SAR). In immunofluorescence assays, an antiviral effect was observed for compound 26 containing a d-homocyclohexylalanine residue in its linker segment. Due to its excellent selectivity profile and low cytotoxicity, this inhibitor scaffold could be a suitable starting point for the development of peptidic drugs against the Zika virus and related flaviviruses.
		+
		+	Structure-Based Optimization and Characterization of Macrocyclic Zika Virus NS2B-NS3 Protease Inhibitors.,Huber S, Braun NJ, Schmacke LC, Quek JP, Murra R, Bender D, Hildt E, Luo D, Heine A, Steinmetzer T J Med Chem. 2022 May 12;65(9):6555-6572. doi: 10.1021/acs.jmedchem.1c01860. Epub , 2022 Apr 27. PMID:35475620<ref>PMID:35475620</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7pfy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Zika virus]]
	[[Category: Heine A]]		[[Category: Heine A]]
	[[Category: Huber S]]		[[Category: Huber S]]
	[[Category: Steinmetzer T]]		[[Category: Steinmetzer T]]

OCA at 10:01, 31 August 2022

2022-08-31T10:01:51Z

←Older revision		Revision as of 10:01, 31 August 2022
Line 1:		Line 1:

-	====	+	==Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus in Complex with Inhibitor MI-2241==
	<StructureSection load='7pfy' size='340' side='right'caption='[[7pfy]]' scene=''>		<StructureSection load='7pfy' size='340' side='right'caption='[[7pfy]]' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PFY 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=7pfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pfy OCA], [https://pdbe.org/7pfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pfy RCSB], [https://www.ebi.ac.uk/pdbsum/7pfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pfy ProSAT]</span></td></tr>		</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=7pfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pfy OCA], [https://pdbe.org/7pfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pfy RCSB], [https://www.ebi.ac.uk/pdbsum/7pfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pfy ProSAT]</span></td></tr>
	</table>		</table>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Heine A]]
		+	[[Category: Huber S]]
		+	[[Category: Steinmetzer T]]

OCA at 04:46, 25 August 2022

2022-08-25T04:46:46Z

←Older revision		Revision as of 04:46, 25 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7pfy ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7pfy' size='340' side='right'caption='[[7pfy]]' scene=''>
-	~~Authors~~: ~~Huber, S~~.~~, Heine, A~~.~~, Steinmetzer, T~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus in Complex with Inhibitor MI~~-~~2241~~	+	</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=7pfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pfy OCA], [https://pdbe.org/7pfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pfy RCSB], [https://www.ebi.ac.uk/pdbsum/7pfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pfy ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Huber~~, S]]	+	__TOC__
-	[[Category: ~~Heine, A~~]]	+	</StructureSection>
-	[[Category: ~~Steinmetzer, T~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 08:08, 15 September 2021

2021-09-15T08:08:38Z

←Older revision		Revision as of 08:08, 15 September 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Huber, S., Heine, A., Steinmetzer, T.		Authors: Huber, S., Heine, A., Steinmetzer, T.

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

2021-08-18T05:04:35Z

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

←Older revision

Revision as of 05:04, 18 August 2021

OCA: New page: '''Unreleased structure''' The entry 7pfy is ON HOLD Authors: Huber, S., Heine, A., Steinmetzer, T. Description: Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus in Comp...

2021-08-18T05:04:34Z

New page: '''Unreleased structure''' The entry 7pfy is ON HOLD Authors: Huber, S., Heine, A., Steinmetzer, T. Description: Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus in Comp...

New page

'''Unreleased structure'''

The entry 7pfy is ON HOLD

Authors: Huber, S., Heine, A., Steinmetzer, T.

Description: Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus in Complex with Inhibitor MI-2241
[[Category: Unreleased Structures]]
[[Category: Huber, S]]
[[Category: Heine, A]]
[[Category: Steinmetzer, T]]