6vgy - Revision history

OCA at 08:12, 11 October 2023

OCA — Wed, 11 Oct 2023 08:12:26 GMT

←Older revision		Revision as of 08:12, 11 October 2023
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	<StructureSection load='6vgy' size='340' side='right'caption='[[6vgy]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='6vgy' size='340' side='right'caption='[[6vgy]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6vgy]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Mers Mers~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VGY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6VGY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vgy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VGY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VGY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QZJ:N~2~-{[(trans-4-ethylcyclohexyl)oxy]carbonyl}-N-{(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-L-leucinamide'>QZJ</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]] 2.05Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">orf1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1335626 MERS])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QZJ:N~2~-{[(trans-4-ethylcyclohexyl)oxy]carbonyl}-N-{(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-L-leucinamide'>QZJ</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=6vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vgy OCA], [~~http~~://pdbe.org/6vgy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6vgy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6vgy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6vgy 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=6vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vgy OCA], [https://pdbe.org/6vgy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vgy RCSB], [https://www.ebi.ac.uk/pdbsum/6vgy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vgy ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/T2B9U0_MERS T2B9U0_MERS] Catalytic subunit of viral RNA capping enzyme which catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. The kinase-like NiRAN domain of NSP12 transfers RNA to the amino terminus of NSP9, forming a covalent RNA-protein intermediate. Subsequently, the NiRAN domain transfers RNA to GDP, forming the core cap structure GpppA-RNA. The NSP14 and NSP16 methyltransferases then add methyl groups to form functional cap structures.[ARBA:ARBA00034461] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[ARBA:ARBA00002182] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[ARBA:ARBA00003443] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[ARBA:ARBA00003115] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[ARBA:ARBA00002840] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[ARBA:ARBA00002960] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[ARBA:ARBA00003070] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[ARBA:ARBA00002697] Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[ARBA:ARBA00003748] Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (By similarity). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (By similarity). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors.[ARBA:ARBA00025521] RNA-directed RNA polymerase that catalyzes the transcription of viral genomic and subgenomic RNAs. Acts in complex with nsp7 and nsp8 to transcribe both the minus and positive strands of genomic RNA. Subgenomic RNAs (sgRNAs) are formed by discontinuous transcription: The polymerase has the ability to pause at transcription-regulating sequences (TRS) and jump to the leader TRS, resulting in a major deletion. This creates a series of subgenomic RNAs that are replicated, transcribed and translated. In addition, Nsp12 is a subunit of the viral RNA capping enzyme that catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. The kinase-like NiRAN domain of NSP12 transfers RNA to the amino terminus of NSP9, forming a covalent RNA-protein intermediate. Subsequently, the NiRAN domain transfers RNA to GDP, and forms the core cap structure GpppA-RNA.[ARBA:ARBA00034462] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.[ARBA:ARBA00003368]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6vgy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6vgy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Mers~~]]	+	[[Category: Middle East respiratory syndrome-related coronavirus]]
-	[[Category: Battaile~~, K P~~]]	+	[[Category: Battaile KP]]
-	[[Category: Chang~~, K O~~]]	+	[[Category: Chang KO]]
-	[[Category: Groutas~~, W C~~]]	+	[[Category: Groutas WC]]
-	[[Category: Kashipathy~~, M M~~]]	+	[[Category: Kashipathy MM]]
-	[[Category: Kim, Y]]	+	[[Category: Kim Y]]
-	[[Category: Lovell, S]]	+	[[Category: Lovell S]]
-	[[Category: Nguyen~~, H N~~]]	+	[[Category: Nguyen HN]]
-	[[Category: Rathnayake~~, A D~~]]	+	[[Category: Rathnayake AD]]
-	[[Category: Zheng, J]]	+	[[Category: Zheng J]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Mers 3cl protease inhhibitor]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 06:36, 19 August 2020

OCA — Wed, 19 Aug 2020 06:36:06 GMT

←Older revision		Revision as of 06:36, 19 August 2020
Line 1:		Line 1:

	==2.05 A resolution structure of MERS 3CL protease in complex with inhibitor 6b==		==2.05 A resolution structure of MERS 3CL protease in complex with inhibitor 6b==
-	<StructureSection load='6vgy' size='340' side='right'caption='[[6vgy]]' scene=''>	+	<StructureSection load='6vgy' size='340' side='right'caption='[[6vgy]], [[Resolution\|resolution]] 2.05Å' 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=6VGY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VGY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vgy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mers Mers]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VGY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VGY FirstGlance]. <br>
-	</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=6vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vgy OCA], [http://pdbe.org/6vgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vgy RCSB], [http://www.ebi.ac.uk/pdbsum/6vgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vgy 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=QZJ:N~2~-{[(trans-4-ethylcyclohexyl)oxy]carbonyl}-N-{(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-L-leucinamide'>QZJ</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">orf1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1335626 MERS])</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=6vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vgy OCA], [http://pdbe.org/6vgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vgy RCSB], [http://www.ebi.ac.uk/pdbsum/6vgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vgy ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pathogenic coronaviruses are a major threat to global public health, as exemplified by Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound one day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.
		+
		+	3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice.,Rathnayake AD, Zheng J, Kim Y, Perera KD, Mackin S, Meyerholz DK, Kashipathy MM, Battaile KP, Lovell S, Perlman S, Groutas WC, Chang KO Sci Transl Med. 2020 Aug 3. pii: scitranslmed.abc5332. doi:, 10.1126/scitranslmed.abc5332. PMID:32747425<ref>PMID:32747425</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6vgy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Battaile KP]]	+	[[Category: Mers]]
-	[[Category: Chang KO]]	+	[[Category: Battaile, K P]]
-	[[Category: Groutas WC]]	+	[[Category: Chang, K O]]
-	[[Category: Kashipathy MM]]	+	[[Category: Groutas, W C]]
-	[[Category: Kim Y]]	+	[[Category: Kashipathy, M M]]
-	[[Category: Lovell S]]	+	[[Category: Kim, Y]]
-	[[Category: Nguyen HN]]	+	[[Category: Lovell, S]]
-	[[Category: Rathnayake AD]]	+	[[Category: Nguyen, H N]]
-	[[Category: Zheng J]]	+	[[Category: Rathnayake, A D]]
		+	[[Category: Zheng, J]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Mers 3cl protease inhhibitor]]
		+	[[Category: Protease]]

OCA at 09:47, 12 August 2020

OCA — Wed, 12 Aug 2020 09:47:26 GMT

←Older revision		Revision as of 09:47, 12 August 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6vgy ~~is ON HOLD until Paper Publication~~	+	==2.05 A resolution structure of MERS 3CL protease in complex with inhibitor 6b==
-		+	<StructureSection load='6vgy' size='340' side='right'caption='[[6vgy]]' scene=''>
-	~~Authors~~: ~~Lovell, S~~.~~, Battaile, K~~.P.~~, Kashipathy, M~~.M.~~, Rathnayake, A~~.D., ~~Zheng, J~~., ~~Kim, Y~~., ~~Nguyen, H~~.N., ~~Chang, K~~.O., ~~Groutas, W~~.C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VGY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VGY FirstGlance]. <br>
-	~~Description: 2.05 A resolution structure of MERS 3CL protease in complex with inhibitor 6b~~	+	</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=6vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vgy OCA], [http://pdbe.org/6vgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vgy RCSB], [http://www.ebi.ac.uk/pdbsum/6vgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vgy ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Groutas, W.C~~]]	+	__TOC__
-	[[Category: ~~Battaile, K.P~~]]	+	</StructureSection>
-	[[Category: ~~Chang, K.O~~]]	+	[[Category: Large Structures]]
-	[[Category: Kashipathy~~, M.M~~]]	+	[[Category: Battaile KP]]
-	[[Category: Kim, Y]]	+	[[Category: Chang KO]]
-	[[Category: ~~Zheng, J~~]]	+	[[Category: Groutas WC]]
-	[[Category: ~~Lovell, S~~]]	+	[[Category: Kashipathy MM]]
-	[[Category: Rathnayake~~, A.D~~]]	+	[[Category: Kim Y]]
-	[[Category: ~~Nguyen, H.N~~]]	+	[[Category: Lovell S]]
		+	[[Category: Nguyen HN]]
		+	[[Category: Rathnayake AD]]
		+	[[Category: Zheng J]]

OCA at 13:33, 29 January 2020

OCA — Wed, 29 Jan 2020 13:33:28 GMT

←Older revision		Revision as of 13:33, 29 January 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Lovell, S., Battaile, K.P., Kashipathy, M.M., Rathnayake, A.D., Zheng, J., Kim, Y., Nguyen, H.N., Chang, K.O., Groutas, W.C.		Authors: Lovell, S., Battaile, K.P., Kashipathy, M.M., Rathnayake, A.D., Zheng, J., Kim, Y., Nguyen, H.N., Chang, K.O., Groutas, W.C.
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	Description: 2.05 A resolution structure of MERS 3CL protease in complex with inhibitor 6b		Description: 2.05 A resolution structure of MERS 3CL protease in complex with inhibitor 6b
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Battaile, K.P]]
-	[[Category: Lovell, S]]
-	[[Category: Nguyen, H.N]]
	[[Category: Groutas, W.C]]		[[Category: Groutas, W.C]]
		+	[[Category: Battaile, K.P]]
	[[Category: Chang, K.O]]		[[Category: Chang, K.O]]
	[[Category: Kashipathy, M.M]]		[[Category: Kashipathy, M.M]]
	[[Category: Kim, Y]]		[[Category: Kim, Y]]
	[[Category: Zheng, J]]		[[Category: Zheng, J]]
		+	[[Category: Lovell, S]]
	[[Category: Rathnayake, A.D]]		[[Category: Rathnayake, A.D]]
		+	[[Category: Nguyen, H.N]]

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

OCA — Wed, 22 Jan 2020 14:26:25 GMT

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

←Older revision

Revision as of 14:26, 22 January 2020

OCA: New page: '''Unreleased structure''' The entry 6vgy is ON HOLD Authors: Lovell, S., Battaile, K.P., Kashipathy, M.M., Rathnayake, A.D., Zheng, J., Kim, Y., Nguyen, H.N., Chang, K.O., Groutas, W.C...

OCA — Wed, 22 Jan 2020 14:26:23 GMT

New page: '''Unreleased structure''' The entry 6vgy is ON HOLD Authors: Lovell, S., Battaile, K.P., Kashipathy, M.M., Rathnayake, A.D., Zheng, J., Kim, Y., Nguyen, H.N., Chang, K.O., Groutas, W.C...

New page

'''Unreleased structure'''

The entry 6vgy is ON HOLD

Authors: Lovell, S., Battaile, K.P., Kashipathy, M.M., Rathnayake, A.D., Zheng, J., Kim, Y., Nguyen, H.N., Chang, K.O., Groutas, W.C.

Description: 2.05 A resolution structure of MERS 3CL protease in complex with inhibitor 6b
[[Category: Unreleased Structures]]
[[Category: Battaile, K.P]]
[[Category: Lovell, S]]
[[Category: Nguyen, H.N]]
[[Category: Groutas, W.C]]
[[Category: Chang, K.O]]
[[Category: Kashipathy, M.M]]
[[Category: Kim, Y]]
[[Category: Zheng, J]]
[[Category: Rathnayake, A.D]]