|
|
| Line 1: |
Line 1: |
|
| |
|
| ==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with PCM-0102277== | | ==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with PCM-0102277== |
| <StructureSection load='5rfh' size='340' side='right'caption='[[5rfh]], [[Resolution|resolution]] 1.58Å' scene=''> | | <StructureSection load='5rfh' size='340' side='right'caption='[[5rfh]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[5rfh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Wcpv Wcpv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5RFH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5RFH FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5RFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5RFH FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=T6Y:1-{4-[(5-chlorothiophen-2-yl)methyl]piperazin-1-yl}ethan-1-one'>T6Y</scene></td></tr> | | </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=5rfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5rfh OCA], [https://pdbe.org/5rfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5rfh RCSB], [https://www.ebi.ac.uk/pdbsum/5rfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5rfh ProSAT]</span></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 WCPV])</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=5rfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5rfh OCA], [http://pdbe.org/5rfh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5rfh RCSB], [http://www.ebi.ac.uk/pdbsum/5rfh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5rfh ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | |
| [[http://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] | | ==See Also== |
| == References ==
| | *[[Virus protease 3D structures|Virus protease 3D structures]] |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Wcpv]]
| | [[Category: Aimon A]] |
| [[Category: Aimon, A]] | | [[Category: Brandao-Neto J]] |
| [[Category: Brandao-Neto, J]] | | [[Category: Carbery A]] |
| [[Category: Carbery, A]] | | [[Category: Douangamath A]] |
| [[Category: Delft, F von]]
| | [[Category: Dunnett L]] |
| [[Category: Douangamath, A]] | | [[Category: Fearon D]] |
| [[Category: Dunnett, L]] | | [[Category: Gehrtz P]] |
| [[Category: Fearon, D]] | | [[Category: Krojer T]] |
| [[Category: Gehrtz, P]] | | [[Category: London N]] |
| [[Category: Krojer, T]] | | [[Category: Lukacik P]] |
| [[Category: London, N]] | | [[Category: Owen CD]] |
| [[Category: Lukacik, P]] | | [[Category: Powell AJ]] |
| [[Category: Owen, C D]] | | [[Category: Resnick E]] |
| [[Category: Powell, A J]] | | [[Category: Skyner R]] |
| [[Category: Resnick, E]] | | [[Category: Snee M]] |
| [[Category: Skyner, R]] | | [[Category: Strain-Damerell CM]] |
| [[Category: Snee, M]] | | [[Category: Walsh MA]] |
| [[Category: Strain-Damerell, C M]] | | [[Category: Wild C]] |
| [[Category: Walsh, M A]] | | [[Category: Von Delft F]] |
| [[Category: Wild, C]] | |
| [[Category: Hydrolase-hydrolase inhibitor complex]] | |
| [[Category: Pandda]]
| |
| [[Category: Sgc - diamond i04-1 fragment screening]]
| |
| [[Category: Xchemexplorer]]
| |