8dzc - Revision history

OCA at 05:53, 5 July 2023

OCA — Wed, 05 Jul 2023 05:53:55 GMT

←Older revision		Revision as of 05:53, 5 July 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8dzc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DZC FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dzc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DZC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=U76:(3,5-difluorophenyl)methyl+{(3S)-1-[(2S)-1-({(2S,3R)-4-(cyclopropylamino)-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-6-oxopiperidin-3-yl}carbamate'>U76</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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=U76:(3,5-difluorophenyl)methyl+{(3S)-1-[(2S)-1-({(2S,3R)-4-(cyclopropylamino)-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-6-oxopiperidin-3-yl}carbamate'>U76</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=8dzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dzc OCA], [https://pdbe.org/8dzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dzc RCSB], [https://www.ebi.ac.uk/pdbsum/8dzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dzc 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=8dzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dzc OCA], [https://pdbe.org/8dzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dzc RCSB], [https://www.ebi.ac.uk/pdbsum/8dzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dzc ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:29, 7 April 2023

OCA — Fri, 07 Apr 2023 06:29:39 GMT

←Older revision		Revision as of 06:29, 7 April 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8dzc is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor 17==
		+	<StructureSection load='8dzc' size='340' side='right'caption='[[8dzc]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8dzc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DZC FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=U76:(3,5-difluorophenyl)methyl+{(3S)-1-[(2S)-1-({(2S,3R)-4-(cyclopropylamino)-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-6-oxopiperidin-3-yl}carbamate'>U76</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=8dzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dzc OCA], [https://pdbe.org/8dzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dzc RCSB], [https://www.ebi.ac.uk/pdbsum/8dzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dzc ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the 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. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	SARS-CoV-2 is still wreaking havoc all over the world with surging morbidity and high mortality. The main protease (Mpro) is essential in the replication of SARS-CoV-2, enabling itself an active target for antiviral development. Herein, we reported the design and synthesis of a new class of peptidomimetics-constrained alpha, gamma-AApeptides, based on which a series of aldehyde and ketoamide inhibitors of the Mpro of SARS-CoV-2 were prepared. The lead compounds showed excellent inhibitory activity in the FRET-based Mpro enzymatic assay not only for the Mpro of SARS-CoV-2 but also for SARS-CoV and MERS-CoV, along with HCoVs like HCoV-OC43, HCoV-229E, HCoV-NL63 and HKU1. The X-ray crystallographic results demonstrated that our compounds form a covalent bond with the catalytic Cys145. They also demonstrated effective antiviral activity against live SARS-CoV-2. Overall, the results suggest that alpha, gamma-AApeptide could be a promising molecular scaffold in designing novel Mpro inhibitors of SARS-CoV-2 and other coronaviruses.

-	~~Authors:~~ Sacco, M., ~~Chen~~, Y.	+	Development of the Safe and Broad-Spectrum Aldehyde and Ketoamide Mpro inhibitors Derived from the Constrained alpha, gamma-AA Peptide Scaffold.,Wang L, Ma C, Sacco MD, Xue S, Mahmoud M, Calcul L, Chen Y, Wang J, Cai J Chemistry. 2023 Mar 15:e202300476. doi: 10.1002/chem.202300476. PMID:36920943<ref>PMID:36920943</ref>

-	~~Description: Crystal structure~~ of the ~~SARS~~-~~CoV~~-~~2 (COVID-19) main protease in complex with inhibitor 17~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Chen, Y]]	+	<div class="pdbe-citations 8dzc" style="background-color:#fffaf0;"></div>
-	[[Category: Sacco, M]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Chen Y]]
		+	[[Category: Sacco M]]

OCA at 05:44, 14 September 2022

OCA — Wed, 14 Sep 2022 05:44:25 GMT

←Older revision		Revision as of 05:44, 14 September 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8dzc is ON HOLD	+	The entry 8dzc is ON HOLD until Paper Publication

	Authors: Sacco, M., Chen, Y.		Authors: Sacco, M., Chen, Y.

OCA: Protected "8dzc" [edit=sysop:move=sysop]

OCA — Thu, 18 Aug 2022 04:06:59 GMT

Protected "8dzc" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:06, 18 August 2022

OCA: New page: '''Unreleased structure''' The entry 8dzc is ON HOLD Authors: Sacco, M., Chen, Y. Description: Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor 17...

OCA — Thu, 18 Aug 2022 04:06:58 GMT

New page: '''Unreleased structure''' The entry 8dzc is ON HOLD Authors: Sacco, M., Chen, Y. Description: Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor 17...

New page

'''Unreleased structure'''

The entry 8dzc is ON HOLD

Authors: Sacco, M., Chen, Y.

Description: Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor 17
[[Category: Unreleased Structures]]
[[Category: Chen, Y]]
[[Category: Sacco, M]]