1p9s

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<StructureSection load='1p9s' size='340' side='right'caption='[[1p9s]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
<StructureSection load='1p9s' size='340' side='right'caption='[[1p9s]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1p9s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvh22 Cvh22]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P9S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1P9S FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1p9s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_coronavirus_229E Human coronavirus 229E]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P9S FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.54&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lvo|1lvo]], [[1p9t|1p9t]], [[1p9u|1p9u]]</div></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9s OCA], [https://pdbe.org/1p9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p9s RCSB], [https://www.ebi.ac.uk/pdbsum/1p9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p9s ProSAT]</span></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11137 CVH22])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1p9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9s OCA], [http://pdbe.org/1p9s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p9s RCSB], [http://www.ebi.ac.uk/pdbsum/1p9s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p9s ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/R1AB_CVH22 R1AB_CVH22]] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products. 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 (By similarity). 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). The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G). The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction (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). NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond (By similarity).
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[https://www.uniprot.org/uniprot/R1A_CVH22 R1A_CVH22] 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 (By similarity). 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).
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</div>
</div>
<div class="pdbe-citations 1p9s" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 1p9s" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Art:Molecular Sculpture|Art:Molecular Sculpture]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Cvh22]]
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[[Category: Human coronavirus 229E]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Anand, K]]
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[[Category: Anand K]]
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[[Category: Hilgenfeld, R]]
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[[Category: Hilgenfeld R]]
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[[Category: Mesters, J R]]
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[[Category: Mesters JR]]
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[[Category: Wadhwani, P]]
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[[Category: Wadhwani P]]
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[[Category: Ziebuhr, J]]
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[[Category: Ziebuhr J]]
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[[Category: Coronavirus]]
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[[Category: Hcov]]
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[[Category: Hydrolase]]
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[[Category: Sars-cov]]
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[[Category: Tgev]]
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Revision as of 09:41, 16 August 2023

Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of anti-SARS Drugs

PDB ID 1p9s

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