5goz - Revision history

OCA at 11:38, 2 August 2023

OCA — Wed, 02 Aug 2023 11:38:28 GMT

←Older revision		Revision as of 11:38, 2 August 2023
Line 3:		Line 3:
	<StructureSection load='5goz' size='340' side='right'caption='[[5goz]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='5goz' size='340' side='right'caption='[[5goz]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5goz]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GOZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5GOZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5goz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Zika_virus Zika virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GOZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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]] 2.049Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5gp1\|5gp1]]~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5goz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5goz OCA], [~~http~~://pdbe.org/5goz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5goz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5goz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5goz 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=5goz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5goz OCA], [https://pdbe.org/5goz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5goz RCSB], [https://www.ebi.ac.uk/pdbsum/5goz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5goz ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POLG_ZIKVF POLG_ZIKVF] Capsid protein C: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions.[UniProtKB:P17763] Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.[UniProtKB:P03314] Peptide pr: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.[UniProtKB:P17763] Protein prM: Plays a role in host immune defense modulation and protection of envelope protein E during virion synthesis. PrM-E cleavage is ineficient, and immature prM-E proteins could have an activity against host immune response. The sequence of PrM contributes to fetal microcephaly in Humans. Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763]<ref>PMID:28971967</ref> Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.[UniProtKB:P17763] Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particule is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763] Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).[UniProtKB:Q9Q6P4] Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response (By similarity). Disrupts adherens junction formation and thereby impairs proliferation of radial cells in both embryonic mouse cortex and human forebrain organoids (PubMed:28826723).[UniProtKB:P14335]<ref>PMID:28826723</ref> Non-structural protein 2B: Required cofactor for the serine protease function of NS3.[UniProtKB:Q32ZE1] Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q32ZE1]<ref>PMID:28592527</ref> Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding (By similarity). Cooperatively with NS4B suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> <ref>PMID:28592527</ref> Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter. Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. 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. Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment (By similarity). Cooperatively with NS4A suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.[UniProtKB:Q9Q6P4]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Jin, T~~]]	+	[[Category: Zika virus]]
-	[[Category: ~~Zhang, C~~]]	+	[[Category: Jin T]]
-	[[Category: ~~Methyltransferase gtp complex]]~~	+	[[Category: Zhang C]]
-	~~[[Category: Transferase~~]]	+

OCA at 06:49, 13 May 2020

OCA — Wed, 13 May 2020 06:49:10 GMT

←Older revision		Revision as of 06:49, 13 May 2020
Line 1:		Line 1:

	==Crystal structure of ZIKV NS5 Methyltransferase in complex with GTP and SAH==		==Crystal structure of ZIKV NS5 Methyltransferase in complex with GTP and SAH==
-	<StructureSection load='5goz' size='340' side='right' caption='[[5goz]], [[Resolution\|resolution]] 2.05Å' scene=''>	+	<StructureSection load='5goz' size='340' side='right'caption='[[5goz]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5goz]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GOZ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5GOZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5goz]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GOZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GOZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5gp1\|5gp1]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5gp1\|5gp1]]</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=5goz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5goz OCA], [http://pdbe.org/5goz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5goz RCSB], [http://www.ebi.ac.uk/pdbsum/5goz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5goz ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5goz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5goz OCA], [http://pdbe.org/5goz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5goz RCSB], [http://www.ebi.ac.uk/pdbsum/5goz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5goz ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 17:		Line 17:
	</div>		</div>
	<div class="pdbe-citations 5goz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5goz" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Jin, T]]		[[Category: Jin, T]]
	[[Category: Zhang, C]]		[[Category: Zhang, C]]
	[[Category: Methyltransferase gtp complex]]		[[Category: Methyltransferase gtp complex]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 19:28, 9 December 2016

OCA — Fri, 09 Dec 2016 19:28:08 GMT

←Older revision		Revision as of 19:28, 9 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5goz is ~~ON HOLD~~	+	==Crystal structure of ZIKV NS5 Methyltransferase in complex with GTP and SAH==
		+	<StructureSection load='5goz' size='340' side='right' caption='[[5goz]], [[Resolution\|resolution]] 2.05Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5goz]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GOZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GOZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5gp1\|5gp1]]</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=5goz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5goz OCA], [http://pdbe.org/5goz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5goz RCSB], [http://www.ebi.ac.uk/pdbsum/5goz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5goz ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Recent outbreak of flavivirus Zika virus (ZIKV) in America has urged the basic as well as translational studies of this important human pathogen. The nonstructural protein 5 (NS5) of the flavivirus has an N-terminal methyltransferase (MTase) domain that plays critical roles in viral RNA genome capping. The null mutant of NS5 MTase is lethal for virus. Therefore, NS5 is a potential drug target for the treatment of Zika virus infection. In this study, we determined crystal structures of the ZIKV MTase in complex with GTP and RNA cap analogue 7meGpppA. Structural analyses revealed highly conserved GTP/cap-binding pocket and S-adenosylmethionine (SAM)-binding pocket. Two conformations of the second base of the cap were identified, which suggests the flexibility of RNA conformation. In addition, the ligand-binding pockets identified a continuous region of hotspots suitable for drug design. Docking calculation shows that the Dengue virus inhibitor compound 10 may bind to the ZIKV MTase.

-	~~Authors: Zhang~~, C., Jin, T.	+	Structure of the NS5 methyltransferase from Zika virus and implications in inhibitor design.,Zhang C, Feng T, Cheng J, Li Y, Yin X, Zeng W, Jin X, Li Y, Guo F, Jin T Biochem Biophys Res Commun. 2016 Nov 17. pii: S0006-291X(16)31963-5. doi:, 10.1016/j.bbrc.2016.11.098. PMID:27866982<ref>PMID:27866982</ref>

-	~~Description: Crystal structure~~ of ~~ZIKV NS5 Methyltransferase in complex with GTP and SAH~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5goz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Jin, T]]		[[Category: Jin, T]]
	[[Category: Zhang, C]]		[[Category: Zhang, C]]
		+	[[Category: Methyltransferase gtp complex]]
		+	[[Category: Transferase]]

OCA: Protected "5goz" [edit=sysop:move=sysop]

OCA — Wed, 10 Aug 2016 11:07:57 GMT

Protected "5goz" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:07, 10 August 2016

OCA: New page: '''Unreleased structure''' The entry 5goz is ON HOLD Authors: Zhang, C., Jin, T. Description: Crystal structure of ZIKV NS5 Methyltransferase in complex with GTP and SAH [[Category: Un...

OCA — Wed, 10 Aug 2016 11:07:56 GMT

New page: '''Unreleased structure''' The entry 5goz is ON HOLD Authors: Zhang, C., Jin, T. Description: Crystal structure of ZIKV NS5 Methyltransferase in complex with GTP and SAH [[Category: Un...

New page

'''Unreleased structure'''

The entry 5goz is ON HOLD

Authors: Zhang, C., Jin, T.

Description: Crystal structure of ZIKV NS5 Methyltransferase in complex with GTP and SAH
[[Category: Unreleased Structures]]
[[Category: Jin, T]]
[[Category: Zhang, C]]