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1p9u

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Revision as of 07:26, 9 December 2020

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

Structural highlights

1p9u is a 8 chain structure with sequence from Porcine transmissable gastroenteritis coronavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:	,
Related:	1lvo, 1p9s, 1p9t
Gene:	ORF1a (Porcine transmissable gastroenteritis coronavirus)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[R1AB_CVPPU] 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-|-[SAGC]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. 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).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (Mpro, also called 3CLpro), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) Mpro and for an inhibitor complex of porcine coronavirus [transmissible gastroenteritis virus (TGEV)] Mpro, and we constructed a homology model for SARS coronavirus (SARS-CoV) Mpro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV Mpro-mediated cleavage of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS.

Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs.,Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R Science. 2003 Jun 13;300(5626):1763-7. Epub 2003 May 13. PMID:12746549^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science. 2003 Jun 13;300(5626):1763-7. Epub 2003 May 13. PMID:12746549 doi:10.1126/science.1085658

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1p9u"

@@ Line 1: / Line 1: @@
 ==Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of anti-SARS Drugs==
-<StructureSection load='1p9u' size='340' side='right' caption='[[1p9u]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
+<StructureSection load='1p9u' size='340' side='right'caption='[[1p9u]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1p9u]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Porcine_transmissable_gastroenteritis_coronavirus Porcine transmissable gastroenteritis coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P9U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P9U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1p9u]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Porcine_transmissable_gastroenteritis_coronavirus Porcine transmissable gastroenteritis coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P9U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1P9U FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lvo|1lvo]], [[1p9s|1p9s]], [[1p9t|1p9t]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lvo|1lvo]], [[1p9s|1p9s]], [[1p9t|1p9t]]</div></td></tr>
 <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=11149 Porcine transmissable gastroenteritis coronavirus])</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=1p9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9u OCA], [http://pdbe.org/1p9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p9u RCSB], [http://www.ebi.ac.uk/pdbsum/1p9u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p9u ProSAT]</span></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=1p9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9u OCA], [http://pdbe.org/1p9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p9u RCSB], [http://www.ebi.ac.uk/pdbsum/1p9u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p9u ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p9/1p9u_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p9/1p9u_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 35: / Line 35: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Porcine transmissable gastroenteritis coronavirus]]
 [[Category: Anand, K]]

1p9u

From Proteopedia

Revision as of 07:26, 9 December 2020

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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