7eo7 - Revision history

OCA at 16:57, 29 November 2023

2023-11-29T16:57:32Z

←Older revision		Revision as of 16:57, 29 November 2023
Line 3:		Line 3:
	<StructureSection load='7eo7' size='340' side='right'caption='[[7eo7]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='7eo7' size='340' side='right'caption='[[7eo7]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7eo7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EO7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7eo7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_coronavirus_NL63 Human coronavirus NL63]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EO7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FNO:2-[(1R)-4-methyl-1-oxidanyl-pent-3-enyl]-5,8-bis(oxidanyl)naphthalene-1,4-dione'>FNO</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]] 2.2491663Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FNO:2-[(1R)-4-methyl-1-oxidanyl-pent-3-enyl]-5,8-bis(oxidanyl)naphthalene-1,4-dione'>FNO</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=7eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eo7 OCA], [https://pdbe.org/7eo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eo7 RCSB], [https://www.ebi.ac.uk/pdbsum/7eo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eo7 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=7eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eo7 OCA], [https://pdbe.org/7eo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eo7 RCSB], [https://www.ebi.ac.uk/pdbsum/7eo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eo7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/R1A_CVHNL R1A_CVHNL]] The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3. The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity). Nsp9 is a ssRNA-binding protein (By similarity).	+	[https://www.uniprot.org/uniprot/R1A_CVHNL R1A_CVHNL] The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3. The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity). Nsp9 is a ssRNA-binding protein (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human coronavirus NL63]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gao~~, H X~~]]	+	[[Category: Gao HX]]
-	[[Category: Li, J]]	+	[[Category: Li J]]
-	[[Category: Zhang, J]]	+	[[Category: Zhang J]]
-	[[Category: Zhang~~, Y T~~]]	+	[[Category: Zhang YT]]
-	[[Category: Zhong~~, F L~~]]	+	[[Category: Zhong FL]]
-	[[Category: Zhou~~, X L]]~~	+	[[Category: Zhou XL]]
-	~~[[Category: Hcov]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 13:03, 4 May 2022

2022-05-04T13:03:35Z

←Older revision		Revision as of 13:03, 4 May 2022
Line 1:		Line 1:

	==Crystal structure of HCoV-NL63 3C-like protease in complex with an inhibitor Shikonin==		==Crystal structure of HCoV-NL63 3C-like protease in complex with an inhibitor Shikonin==
-	<StructureSection load='7eo7' size='340' side='right'caption='[[7eo7]]' scene=''>	+	<StructureSection load='7eo7' size='340' side='right'caption='[[7eo7]], [[Resolution\|resolution]] 2.25Å' 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=7EO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EO7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7eo7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EO7 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=7eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eo7 OCA], [https://pdbe.org/7eo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eo7 RCSB], [https://www.ebi.ac.uk/pdbsum/7eo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eo7 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=FNO:2-[(1R)-4-methyl-1-oxidanyl-pent-3-enyl]-5,8-bis(oxidanyl)naphthalene-1,4-dione'>FNO</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=7eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eo7 OCA], [https://pdbe.org/7eo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eo7 RCSB], [https://www.ebi.ac.uk/pdbsum/7eo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eo7 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/R1A_CVHNL R1A_CVHNL]] The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3. The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity). Nsp9 is a ssRNA-binding protein (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Over the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (M(pro); also known as 3CL(pro)) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anti-coronavirus agents. We solved the crystal structures of the main protease of SARS-CoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.
		+
		+	Structure-Based Discovery and Structural Basis of a Novel Broad-Spectrum Natural Product against the Main Protease of Coronavirus.,Zhang Y, Gao H, Hu X, Wang Q, Zhong F, Zhou X, Lin C, Yang Y, Wei J, Du W, Huang H, Zhou H, He W, Zhang H, Zhang Y, McCormick PJ, Fu J, Wang D, Fu Y, Lu X, Zhang T, Duan J, Qin B, Jiang H, Luo J, Zhang Y, Chen Q, Luo Q, Cheng L, Zhang Z, Zhang J, Li J J Virol. 2022 Jan 12;96(1):e0125321. doi: 10.1128/JVI.01253-21. Epub 2021 Sep 29. PMID:34586857<ref>PMID:34586857</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7eo7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gao HX]]	+	[[Category: Gao, H X]]
-	[[Category: Li J]]	+	[[Category: Li, J]]
-	[[Category: Zhang J]]	+	[[Category: Zhang, J]]
-	[[Category: Zhang YT]]	+	[[Category: Zhang, Y T]]
-	[[Category: Zhong FL]]	+	[[Category: Zhong, F L]]
-	[[Category: Zhou XL]]	+	[[Category: Zhou, X L]]
		+	[[Category: Hcov]]
		+	[[Category: Viral protein]]

OCA at 16:28, 20 October 2021

2021-10-20T16:28:30Z

←Older revision		Revision as of 16:28, 20 October 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7eo7 ~~is ON HOLD~~	+	==Crystal structure of HCoV-NL63 3C-like protease in complex with an inhibitor Shikonin==
-		+	<StructureSection load='7eo7' size='340' side='right'caption='[[7eo7]]' scene=''>
-	~~Authors~~: ~~Gao, H~~.X.~~, Zhang, Y~~.T., ~~Zhou, X~~.L., ~~Zhong~~, F.L., ~~Li, J~~., ~~Zhang, J~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EO7 FirstGlance]. <br>
-	~~Description: Crystal structure of HCoV-NL63 3C-like protease in complex with an inhibitor Shikonin~~	+	</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=7eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eo7 OCA], [https://pdbe.org/7eo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eo7 RCSB], [https://www.ebi.ac.uk/pdbsum/7eo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eo7 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Gao~~, H.X~~]]	+	__TOC__
-	[[Category: ~~Zhang, Y.T~~]]	+	</StructureSection>
-	[[Category: ~~Li,~~ J]]	+	[[Category: Large Structures]]
-	[[Category: ~~Zhong, F.L~~]]	+	[[Category: Gao HX]]
-	[[Category: ~~Zhang, J~~]]	+	[[Category: Li J]]
-	[[Category: Zhou~~, X.L~~]]	+	[[Category: Zhang J]]
		+	[[Category: Zhang YT]]
		+	[[Category: Zhong FL]]
		+	[[Category: Zhou XL]]

OCA: Protected "7eo7" [edit=sysop:move=sysop]

2021-04-28T04:13:02Z

Protected "7eo7" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:13, 28 April 2021

OCA: New page: '''Unreleased structure''' The entry 7eo7 is ON HOLD Authors: Gao, H.X., Zhang, Y.T., Zhou, X.L., Zhong, F.L., Li, J., Zhang, J. Description: Crystal structure of HCoV-NL63 3C-like pro...

2021-04-28T04:13:00Z

New page: '''Unreleased structure''' The entry 7eo7 is ON HOLD Authors: Gao, H.X., Zhang, Y.T., Zhou, X.L., Zhong, F.L., Li, J., Zhang, J. Description: Crystal structure of HCoV-NL63 3C-like pro...

New page

'''Unreleased structure'''

The entry 7eo7 is ON HOLD

Authors: Gao, H.X., Zhang, Y.T., Zhou, X.L., Zhong, F.L., Li, J., Zhang, J.

Description: Crystal structure of HCoV-NL63 3C-like protease in complex with an inhibitor Shikonin
[[Category: Unreleased Structures]]
[[Category: Gao, H.X]]
[[Category: Zhang, Y.T]]
[[Category: Li, J]]
[[Category: Zhong, F.L]]
[[Category: Zhang, J]]
[[Category: Zhou, X.L]]