OCA at 10:55, 15 November 2023

2023-11-15T10:55:39Z

← Older revision		Revision as of 10:55, 15 November 2023
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	====		==Crystal structure of Zika NS2B-NS3 protease with compound 5==
	<StructureSection load='7doc' size='340' side='right'caption='[[7doc]]' scene=''>		<StructureSection load='7doc' size='340' side='right'caption='[[7doc]], [[Resolution\|resolution]] 1.90Å' 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'>[[7doc]] is a 9 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=7DOC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DOC 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=7doc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7doc OCA], [https://pdbe.org/7doc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7doc RCSB], [https://www.ebi.ac.uk/pdbsum/7doc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7doc 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]] 1.904Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HHC:~{N}-[(2~{R})-2,3-bis(azanyl)-3-oxidanylidene-propyl]-2-[(4~{R})-4-methanoyl-4,5-dihydro-1,3-thiazol-2-yl]pyridine-4-carboxamide'>HHC</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=7doc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7doc OCA], [https://pdbe.org/7doc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7doc RCSB], [https://www.ebi.ac.uk/pdbsum/7doc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7doc 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 ==
			The rapid generation and modification of macrocyclic peptides in medicinal chemistry is an ever-growing area that can present various synthetic challenges. The reaction between N-terminal cysteine and 2-cyanoisonicotinamide is a new biocompatible click reaction that allows rapid access to macrocyclic peptides. Importantly, 2-cyanoisonicotinamide can be attached to different linkers directly during solid-phase peptide synthesis. The synthesis involves only commercially available precursors, allowing for a fully automated process. We demonstrate the approach for four cyclic peptide ligands of the Zika virus protease NS2B-NS3. Although all peptides display the substrate recognition motif, the activity strongly depends on the linker length, with the shortest cyclization linker corresponding to highest activity (K (i) = 0.64 muM). The most active cyclic peptide displays affinity 78 times higher than that of its linear analogue. We solved a crystal structure of the proteolytically cleaved ligand and synthesized it by applying the presented chemistry to peptide ligation.

			2-Cyanoisonicotinamide Conjugation: A Facile Approach to Generate Potent Peptide Inhibitors of the Zika Virus Protease.,Patil NA, Quek JP, Schroeder B, Morewood R, Rademann J, Luo D, Nitsche C ACS Med Chem Lett. 2021 Mar 31;12(5):732-737. doi: , 10.1021/acsmedchemlett.0c00657. eCollection 2021 May 13. PMID:34055219<ref>PMID:34055219</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7doc" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Z-disk~~]]		[[Category: Synthetic construct]]
			[[Category: Zika virus]]
			[[Category: Quek JP]]

OCA at 06:47, 14 April 2021

2021-04-14T06:47:09Z

← Older revision		Revision as of 06:47, 14 April 2021
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7doc is ~~ON HOLD until Paper Publication~~		====
			<StructureSection load='7doc' size='340' side='right'caption='[[7doc]]' scene=''>
	~~Authors~~: ~~Quek~~, J.P.		== 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 Zika NS2B-NS3 protease with compound 5~~		</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=7doc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7doc OCA], [https://pdbe.org/7doc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7doc RCSB], [https://www.ebi.ac.uk/pdbsum/7doc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7doc ProSAT]</span></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		</table>
	[[Category: ~~Quek, J.P~~]]		__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Z-disk]]

OCA at 14:27, 10 March 2021

2021-03-10T14:27:51Z

← Older revision		Revision as of 14:27, 10 March 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7doc is ON HOLD		The entry 7doc is ON HOLD until Paper Publication

	Authors: Quek, J.P.		Authors: Quek, J.P.

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

2020-12-24T07:54:51Z

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

← Older revision	Revision as of 07:54, 24 December 2020
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7doc is ON HOLD Authors: Quek, J.P. Description: Crystal structure of Zika NS2B-NS3 protease with compound 5 Category: Unreleased Structures [[...

2020-12-24T07:54:49Z

New page: '''Unreleased structure''' The entry 7doc is ON HOLD Authors: Quek, J.P. Description: Crystal structure of Zika NS2B-NS3 protease with compound 5 Category: Unreleased Structures [[...

New page

'''Unreleased structure'''

The entry 7doc is ON HOLD

Authors: Quek, J.P.

Description: Crystal structure of Zika NS2B-NS3 protease with compound 5
[[Category: Unreleased Structures]]
[[Category: Quek, J.P]]

7doc - Revision history

OCA at 10:55, 15 November 2023

OCA at 06:47, 14 April 2021

OCA at 14:27, 10 March 2021

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

OCA: New page: '''Unreleased structure''' The entry 7doc is ON HOLD Authors: Quek, J.P. Description: Crystal structure of Zika NS2B-NS3 protease with compound 5 Category: Unreleased Structures [[...