View source for 7ap6


==Structure of SARS-CoV-2 Main Protease bound to MUT056399.==
<StructureSection load='7ap6' size='340' side='right'caption='[[7ap6]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ap6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AP6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AP6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RQN:4-(4-ethyl-5-fluoranyl-2-oxidanyl-phenoxy)-3-fluoranyl-benzamide'>RQN</scene></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 2019-nCoV])</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=7ap6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ap6 OCA], [http://pdbe.org/7ap6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7ap6 RCSB], [http://www.ebi.ac.uk/pdbsum/7ap6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7ap6 ProSAT]</span></td></tr>
</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] 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: 2019-ncov]]
[[Category: Large Structures]]
[[Category: Awel, S]]
[[Category: Beck, T]]
[[Category: Betzel, C]]
[[Category: Brehm, W]]
[[Category: Brognaro, H]]
[[Category: Chapman, H N]]
[[Category: Chari, A]]
[[Category: Domaracky, M]]
[[Category: Doyle, J J]]
[[Category: Dunkel, I]]
[[Category: Ehrt, C]]
[[Category: Ellinger, B]]
[[Category: Esperanza, G Pena]]
[[Category: Ewert, W]]
[[Category: Falke, S]]
[[Category: Feiler, C]]
[[Category: Fischer, P]]
[[Category: Fleckenstein, H]]
[[Category: Franca, B Alves]]
[[Category: Galchenkova, M]]
[[Category: Garcia, Y Fernandez]]
[[Category: Gelisio, L]]
[[Category: Gevorkov, Y]]
[[Category: Ginn, H]]
[[Category: Giseler, H]]
[[Category: Gribbon, P]]
[[Category: Groessler, M]]
[[Category: Guenther, S]]
[[Category: Hakanpaeae, J]]
[[Category: Han, H]]
[[Category: Hennicke, V]]
[[Category: Hilgenfeld, R]]
[[Category: Knoska, J]]
[[Category: Koua, F]]
[[Category: Kuzikov, M]]
[[Category: Lane, T J]]
[[Category: Li, C]]
[[Category: Lieske, J]]
[[Category: Lorenzen, K]]
[[Category: Mashour, A Rahmani]]
[[Category: Meents, A]]
[[Category: Mehrabi, P]]
[[Category: Meier, S]]
[[Category: Melo, D]]
[[Category: Meyer, J]]
[[Category: Noei, H]]
[[Category: Norton-Baker, B]]
[[Category: Oberthuer, D]]
[[Category: Paulraj, L X]]
[[Category: Pearson, A]]
[[Category: Peck, A]]
[[Category: Perbandt, M]]
[[Category: Pletzer-Zelgert, J]]
[[Category: Rarey, M]]
[[Category: Reinke, P]]
[[Category: Saouane, S]]
[[Category: Schmidt, C]]
[[Category: Schubert, R]]
[[Category: Schulz, E C]]
[[Category: Schwinzer, M]]
[[Category: Seychell, B]]
[[Category: Tidow, H]]
[[Category: Tolstikova, A]]
[[Category: Trost, F]]
[[Category: Turk, D]]
[[Category: Ullah, N]]
[[Category: Weiss, M]]
[[Category: Werner, N]]
[[Category: White, T A]]
[[Category: Wolf, M]]
[[Category: Wollenhaupt, J]]
[[Category: Yefanov, O]]
[[Category: Zaliani, A]]
[[Category: Zhang, L]]
[[Category: Covid-!9]]
[[Category: Mpro]]
[[Category: Peptide binding protein]]
[[Category: Sars-cov-2]]