3sne - Revision history

OCA at 08:02, 29 June 2022

OCA — Wed, 29 Jun 2022 08:02:52 GMT

←Older revision		Revision as of 08:02, 29 June 2022
Line 1:		Line 1:

	==Crystal structure of SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaking)==		==Crystal structure of SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaking)==
-	<StructureSection load='3sne' size='340' side='right' caption='[[3sne]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='3sne' size='340' side='right'caption='[[3sne]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3sne]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3SNE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3sne]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SNE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ECC:(4S)-4-AMINO-5-HYDROXYPENTANAMIDE'>ECC</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ECC:(4S)-4-AMINO-5-HYDROXYPENTANAMIDE'>ECC</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h2z\|2h2z]], [[3sn8\|3sn8]], [[3sna\|3sna]], [[3snb\|3snb]], [[3snc\|3snc]], [[3snd\|3snd]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2h2z\|2h2z]], [[3sn8\|3sn8]], [[3sna\|3sna]], [[3snb\|3snb]], [[3snc\|3snc]], [[3snd\|3snd]]</div></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=3sne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sne OCA], [~~http~~://pdbe.org/3sne PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3sne RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3sne PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3sne 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=3sne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sne OCA], [https://pdbe.org/3sne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sne RCSB], [https://www.ebi.ac.uk/pdbsum/3sne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sne ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/R1A_CVHSA R1A_CVHSA]] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> 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 (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>	+	[[https://www.uniprot.org/uniprot/R1A_CVHSA R1A_CVHSA]] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> 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 (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3sne" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3sne" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Cvhsa]]		[[Category: Cvhsa]]
		+	[[Category: Large Structures]]
	[[Category: Hilgenfeld, R]]		[[Category: Hilgenfeld, R]]
	[[Category: Zhu, L]]		[[Category: Zhu, L]]

OCA at 22:33, 4 August 2016

OCA — Thu, 04 Aug 2016 22:33:49 GMT

←Older revision		Revision as of 22:33, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaking)==		==Crystal structure of SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaking)==
	<StructureSection load='3sne' size='340' side='right' caption='[[3sne]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='3sne' size='340' side='right' caption='[[3sne]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3sne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Sars_coronavirus Sars coronavirus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SNE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3sne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SNE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ECC:(4S)-4-AMINO-5-HYDROXYPENTANAMIDE'>ECC</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ECC:(4S)-4-AMINO-5-HYDROXYPENTANAMIDE'>ECC</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h2z\|2h2z]], [[3sn8\|3sn8]], [[3sna\|3sna]], [[3snb\|3snb]], [[3snc\|3snc]], [[3snd\|3snd]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h2z\|2h2z]], [[3sn8\|3sn8]], [[3sna\|3sna]], [[3snb\|3snb]], [[3snc\|3snc]], [[3snd\|3snd]]</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=3sne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sne OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sne RCSB], [http://www.ebi.ac.uk/pdbsum/3sne 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=3sne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sne OCA], [http://pdbe.org/3sne PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sne RCSB], [http://www.ebi.ac.uk/pdbsum/3sne PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sne ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 3sne" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Sars coronavirus~~]]	+	[[Category: Cvhsa]]
	[[Category: Hilgenfeld, R]]		[[Category: Hilgenfeld, R]]
	[[Category: Zhu, L]]		[[Category: Zhu, L]]

OCA at 13:40, 25 December 2014

OCA — Thu, 25 Dec 2014 13:40:40 GMT

←Older revision		Revision as of 13:40, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3sne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SNE FirstGlance]. <br>		<table><tr><td colspan='2'>[[3sne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SNE FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ECC:(4S)-4-AMINO-5-HYDROXYPENTANAMIDE'>ECC</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ECC:(4S)-4-AMINO-5-HYDROXYPENTANAMIDE'>ECC</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h2z\|2h2z]], [[3sn8\|3sn8]], [[3sna\|3sna]], [[3snb\|3snb]], [[3snc\|3snc]], [[3snd\|3snd]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h2z\|2h2z]], [[3sn8\|3sn8]], [[3sna\|3sna]], [[3snb\|3snb]], [[3snc\|3snc]], [[3snd\|3snd]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sne OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sne RCSB], [http://www.ebi.ac.uk/pdbsum/3sne 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=3sne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sne OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sne RCSB], [http://www.ebi.ac.uk/pdbsum/3sne PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/R1A_CVHSA R1A_CVHSA]] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> 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 (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 14:		Line 16:
	Peptide aldehyde inhibitors challenge the substrate specificity of the SARS-coronavirus main protease.,Zhu L, George S, Schmidt MF, Al-Gharabli SI, Rademann J, Hilgenfeld R Antiviral Res. 2011 Aug 11. PMID:21854807<ref>PMID:21854807</ref>		Peptide aldehyde inhibitors challenge the substrate specificity of the SARS-coronavirus main protease.,Zhu L, George S, Schmidt MF, Al-Gharabli SI, Rademann J, Hilgenfeld R Antiviral Res. 2011 Aug 11. PMID:21854807<ref>PMID:21854807</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
	== References ==		== References ==
Line 21:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
-	[[Category: Hilgenfeld, R.]]	+	[[Category: Hilgenfeld, R]]
-	[[Category: Zhu, L.]]	+	[[Category: Zhu, L]]
	[[Category: 3c-like proteinase]]		[[Category: 3c-like proteinase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 05:31, 5 June 2014

OCA — Thu, 05 Jun 2014 05:31:15 GMT

←Older revision		Revision as of 05:31, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~3sne.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaking)==
		+	<StructureSection load='3sne' size='340' side='right' caption='[[3sne]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3sne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SNE FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ECC:(4S)-4-AMINO-5-HYDROXYPENTANAMIDE'>ECC</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2h2z\|2h2z]], [[3sn8\|3sn8]], [[3sna\|3sna]], [[3snb\|3snb]], [[3snc\|3snc]], [[3snd\|3snd]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sne OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sne RCSB], [http://www.ebi.ac.uk/pdbsum/3sne PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	SARS coronavirus main protease (SARS-CoV M(pro)) is essential for the replication of the virus and regarded as a major antiviral drug target. The enzyme is a cysteine protease, with a catalytic dyad (Cys-145/His-41) in the active site. Aldehyde inhibitors can bind reversibly to the active-site sulfhydryl of SARS-CoV M(pro). Previous studies using peptidic substrates and inhibitors showed that the substrate specificity of SARS-CoV M(pro) requires glutamine in the P1 position and a large hydrophobic residue in the P2 position. We determined four crystal structures of SARS-CoV M(pro) in complex with pentapeptide aldehydes (Ac-ESTLQ-H, Ac-NSFSQ-H, Ac-DSFDQ-H, and Ac-NSTSQ-H). Kinetic data showed that all of these aldehydes exhibit inhibitory activity towards SARS-CoV M(pro), with K(i) values in the muM range. Surprisingly, the X-ray structures revealed that the hydrophobic S2 pocket of the enzyme can accommodate serine and even aspartic-acid side-chains in the P2 positions of the inhibitors. Consequently, we reassessed the substrate specificity of the enzyme by testing the cleavage of 20 different tetradecapeptide substrates with varying amino-acid residues in the P2 position. The cleavage efficiency for the substrate with serine in the P2 position was 160-times lower than that for the original substrate (P2=Leu); furthermore, the substrate with aspartic acid in the P2 position was not cleaved at all. We also determined a crystal structure of SARS-CoV M(pro) in complex with aldehyde Cm-FF-H, which has its P1-phenylalanine residue bound to the relatively hydrophilic S1 pocket of the enzyme and yet exhibits a high inhibitory activity against SARS-CoV M(pro), with K(i)=2.24+/-0.58muM. These results show that the stringent substrate specificity of the SARS-CoV M(pro) with respect to the P1 and P2 positions can be overruled by the highly electrophilic character of the aldehyde warhead, thereby constituting a deviation from the dogma that peptidic inhibitors need to correspond to the observed cleavage specificity of the target protease.

-	<!--	+	Peptide aldehyde inhibitors challenge the substrate specificity of the SARS-coronavirus main protease.,Zhu L, George S, Schmidt MF, Al-Gharabli SI, Rademann J, Hilgenfeld R Antiviral Res. 2011 Aug 11. PMID:21854807<ref>PMID:21854807</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3sne"~~, ~~creates the "Structure Box" on the page~~.	+
-	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~	+
-	~~or leave the SCENE parameter empty for the default display~~.	+
-	-->	+
-	~~{{STRUCTURE_3sne\| PDB=3sne \| SCENE= }}~~	+

-	~~===Crystal structure~~ of ~~SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaking)===~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-		+	== References ==
-	~~<!--~~	+	<references/>
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21854807}}, adds~~ the ~~Publication Abstract to the page~~	+	__TOC__
-	~~(as it appears on PubMed at http://www~~.~~pubmed~~.~~gov), where 21854807 is the PubMed ID number~~.	+	</StructureSection>
-	-->	+
-	~~{{ABSTRACT_PUBMED_21854807}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3sne]] is a 2 chain structure with sequence from [http:~~/~~/en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA].~~	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:021854807<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Hilgenfeld, R.]]		[[Category: Hilgenfeld, R.]]

OCA at 05:47, 14 September 2011

OCA — Wed, 14 Sep 2011 05:47:46 GMT

←Older revision		Revision as of 05:47, 14 September 2011
Line 1:		Line 1:
-	[[Image:3sne.~~jpg~~\|left\|200px]]	+	[[Image:3sne.png\|left\|200px]]

	<!--		<!--
Line 9:		Line 9:
	{{STRUCTURE_3sne\| PDB=3sne \| SCENE= }}		{{STRUCTURE_3sne\| PDB=3sne \| SCENE= }}

-	===~~The crystal~~ structure of ~~the~~ SARS coronavirus main protease complexed with Ac-ESTLQ-H (~~Soaked~~)===	+	===Crystal structure of SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaking)===

OCA at 06:12, 7 September 2011

OCA — Wed, 07 Sep 2011 06:12:11 GMT

←Older revision		Revision as of 06:12, 7 September 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3sne.jpg\|left\|200px]]

-	The ~~entry 3sne~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3sne", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3sne\| PDB=3sne \| SCENE= }}

-	~~Authors: Zhu, L., Hilgenfeld, R.~~	+	===The crystal structure of the SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaked)===

-	~~Description:~~ The ~~crystal structure of~~ the ~~SARS coronavirus main protease complexed~~ with Ac-~~ESTLQ~~-~~H (Soaked)~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21854807}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21854807 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21854807}}
		+
		+	==About this Structure==
		+	[[3sne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNE OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021854807</ref><references group="xtra"/>
		+	[[Category: Sars coronavirus]]
		+	[[Category: Hilgenfeld, R.]]
		+	[[Category: Zhu, L.]]
		+	[[Category: 3c-like proteinase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Inhibitor ac-estlq-h]]
		+	[[Category: Protease]]
		+	[[Category: Sars coronavirus main protease]]

OCA at 05:48, 17 August 2011

OCA — Wed, 17 Aug 2011 05:48:42 GMT

←Older revision		Revision as of 05:48, 17 August 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3sne is ON HOLD	+	The entry 3sne is ON HOLD until Paper Publication

	Authors: Zhu, L., Hilgenfeld, R.		Authors: Zhu, L., Hilgenfeld, R.

	Description: The crystal structure of the SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaked)		Description: The crystal structure of the SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaked)

OCA at 05:40, 27 July 2011

OCA — Wed, 27 Jul 2011 05:40:18 GMT

←Older revision		Revision as of 05:40, 27 July 2011
Line 3:		Line 3:
	The entry 3sne is ON HOLD		The entry 3sne is ON HOLD

-	Authors: ~~Lili~~,Z, ~~Rolf~~,H	+	Authors: Zhu, L., Hilgenfeld, R.

-	Description: ~~the~~ crystal structure of the SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaked)	+	Description: The crystal structure of the SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaked)

OCA: Protected "3sne" [edit=sysop:move=sysop]

OCA — Wed, 06 Jul 2011 18:29:45 GMT

Protected "3sne" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:29, 6 July 2011

OCA: New page: '''Unreleased structure''' The entry 3sne is ON HOLD Authors: Lili,Z, Rolf,H Description: the crystal structure of the SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaked)

OCA — Wed, 06 Jul 2011 18:29:44 GMT

New page: '''Unreleased structure''' The entry 3sne is ON HOLD Authors: Lili,Z, Rolf,H Description: the crystal structure of the SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaked)

New page

'''Unreleased structure'''

The entry 3sne is ON HOLD

Authors: Lili,Z, Rolf,H

Description: the crystal structure of the SARS coronavirus main protease complexed with Ac-ESTLQ-H (Soaked)