4rsp - Revision history

OCA at 17:54, 20 September 2023

2023-09-20T17:54:32Z

←Older revision		Revision as of 17:54, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rsp]] 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=4RSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RSP FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rsp]] 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=4RSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RSP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CEV:ETHYL+(4R)-4-AMINO-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>CEV</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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]] 1.62Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CEV:ETHYL+(4R)-4-AMINO-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>CEV</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [https://pdbe.org/4rsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [https://www.ebi.ac.uk/pdbsum/4rsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rsp 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=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [https://pdbe.org/4rsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [https://www.ebi.ac.uk/pdbsum/4rsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rsp ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:27, 8 March 2023

2023-03-08T08:27:16Z

←Older revision		Revision as of 08:27, 8 March 2023
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	<StructureSection load='4rsp' size='340' side='right'caption='[[4rsp]], [[Resolution\|resolution]] 1.62Å' scene=''>		<StructureSection load='4rsp' size='340' side='right'caption='[[4rsp]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rsp]] 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=4RSP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RSP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rsp]] 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=4RSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RSP FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CEV:ETHYL+(4R)-4-AMINO-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>CEV</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CEV:ETHYL+(4R)-4-AMINO-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>CEV</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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'>[https://proteopedia.org/fgij/fg.htm?mol=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [https://pdbe.org/4rsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [https://www.ebi.ac.uk/pdbsum/4rsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rsp ProSAT]</span></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=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [~~http~~://pdbe.org/4rsp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rsp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rsp ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/V9TU12_MERS V9TU12_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]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
-	*[[~~SARS Coronavirus Main Proteinase~~\|~~SARS Coronavirus Main Proteinase~~]]	+	*[[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: Mesecar~~, A D~~]]	+	[[Category: Mesecar AD]]
-	[[Category: Tomar, S]]	+	[[Category: Tomar S]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 10:34, 1 May 2019

2019-05-01T10:34:59Z

←Older revision		Revision as of 10:34, 1 May 2019
Line 1:		Line 1:
		+
	==X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor==		==X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor==
-	<StructureSection load='4rsp' size='340' side='right' caption='[[4rsp]], [[Resolution\|resolution]] 1.62Å' scene=''>	+	<StructureSection load='4rsp' size='340' side='right'caption='[[4rsp]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rsp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RSP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RSP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rsp]] 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=4RSP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RSP FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CEV:ETHYL+(4R)-4-AMINO-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>CEV</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CEV:ETHYL+(4R)-4-AMINO-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>CEV</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></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=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [http://www.ebi.ac.uk/pdbsum/4rsp PDBsum]</span></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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [http://pdbe.org/4rsp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [http://www.ebi.ac.uk/pdbsum/4rsp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rsp ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 14:		Line 16:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4rsp" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Mers]]
	[[Category: Mesecar, A D]]		[[Category: Mesecar, A D]]
	[[Category: Tomar, S]]		[[Category: Tomar, S]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Protease]]		[[Category: Protease]]

OCA at 12:10, 1 July 2015

2015-07-01T12:10:54Z

←Older revision		Revision as of 12:10, 1 July 2015
Line 6:		Line 6:
	<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=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [http://www.ebi.ac.uk/pdbsum/4rsp PDBsum]</span></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=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [http://www.ebi.ac.uk/pdbsum/4rsp PDBsum]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the beta-CoV subgroup, require the proteolytic activity of nsp5 protease (aka 3C-like protease, 3CLpro) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CLpro from other beta-CoV 2c members including HKU4 and HKU5, MERS-CoV 3CLpro is less efficient at processing a peptide substrate due to MERS-CoV 3CLpro being a weakly associated dimer. Conversely, HKU4, HKU5 and SARS-CoV 3CLpro enzymes are tightly associated dimers. AUC studies support that MERS-CoV 3CLpro is a weakly associated dimer (Kd ~ 52 mu) with a slow off-rate. Peptidomimetic inhibitors of MERS-CoV 3CLpro were synthesized and utilized in AUC experiments and demonstrate that MERS-CoV 3CLpro undergoes significant ligand-induced dimerization. Kinetic studies also revealed that designed reversible inhibitors act as activators at low compound concentration as a result of induced dimerization. Primary sequence comparisons and X-ray structural analyses of two MERS-CoV 3CLpro-inhibitor complexes, determined to 1.6 A, reveal remarkable structural similarity of the dimer interface with 3CLpro from HKU4-CoV and HKU5-CoV. Despite this structural similarity, substantial differences in the dimerization ability suggest that long-range interactions by the non-conserved amino acids distant from the dimer interface may control MERS-CoV 3CLpro dimerization. Activation of MERS-CoV 3CLpro through ligand-induced dimerization appears to be unique within the genogroup 2c and may potentially increase the complexity in the development of MERS-CoV 3CLpro inhibitors as antiviral agents.
		+
		+	Ligand-induced dimerization of MERS coronavirus nsp5 protease (3CLpro): implications for nsp5 regulation and the development of antivirals.,Tomar S, Johnston ML, St John SE, Osswald HL, Nyalapatla PR, Paul LN, Ghosh AK, Denison MR, Mesecar AD J Biol Chem. 2015 Jun 8. pii: jbc.M115.651463. PMID:26055715<ref>PMID:26055715</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 15:21, 17 June 2015

2015-06-17T15:21:43Z

←Older revision		Revision as of 15:21, 17 June 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor==
-		+	<StructureSection load='4rsp' size='340' side='right' caption='[[4rsp]], [[Resolution\|resolution]] 1.62Å' scene=''>
-	~~The entry~~ 4rsp is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4rsp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RSP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RSP FirstGlance]. <br>
-	~~Authors~~: ~~Tomar, S~~.~~, Mesecar, A~~.D.	+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CEV:ETHYL+(4R)-4-AMINO-5-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTANOATE'>CEV</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></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=4rsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rsp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rsp RCSB], [http://www.ebi.ac.uk/pdbsum/4rsp PDBsum]</span></td></tr>
-	~~Description~~: X-~~ray structure of MERS~~-~~CoV nsp5 protease bound with a designed inhibitor~~	+	</table>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	__TOC__
-	[[Category: Mesecar, A.D]]	+	</StructureSection>
		+	[[Category: Mesecar, A D]]
	[[Category: Tomar, S]]		[[Category: Tomar, S]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Protease]]

OCA at 17:18, 24 December 2014

2014-12-24T17:18:30Z

←Older revision		Revision as of 17:18, 24 December 2014
Line 6:		Line 6:

	Description: X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor		Description: X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor
		+	[[Category: Unreleased Structures]]
		+	[[Category: Mesecar, A.D]]
		+	[[Category: Tomar, S]]

OCA at 06:46, 26 November 2014

2014-11-26T06:46:01Z

←Older revision		Revision as of 06:46, 26 November 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4rsp is ON HOLD	+	The entry 4rsp is ON HOLD until Paper Publication

	Authors: Tomar, S., Mesecar, A.D.		Authors: Tomar, S., Mesecar, A.D.

	Description: X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor		Description: X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor

OCA: Protected "4rsp" [edit=sysop:move=sysop]

2014-11-19T11:33:17Z

Protected "4rsp" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:33, 19 November 2014

OCA: New page: '''Unreleased structure''' The entry 4rsp is ON HOLD Authors: Tomar, S., Mesecar, A.D. Description: X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor

2014-11-19T11:33:15Z

New page: '''Unreleased structure''' The entry 4rsp is ON HOLD Authors: Tomar, S., Mesecar, A.D. Description: X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor

New page

'''Unreleased structure'''

The entry 4rsp is ON HOLD

Authors: Tomar, S., Mesecar, A.D.

Description: X-ray structure of MERS-CoV nsp5 protease bound with a designed inhibitor