1lvo

From Proteopedia

(Difference between revisions)

Revision as of 12:13, 12 October 2017

Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain

Structural highlights

1lvo is a 6 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:	, ,
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

The key enzyme in coronavirus polyprotein processing is the viral main proteinase, M(pro), a protein with extremely low sequence similarity to other viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus M(pro) is reported. The structure was refined to 1.96 A resolution and revealed three dimers in the asymmetric unit. The mutual arrangement of the protomers in each of the dimers suggests that M(pro) self-processing occurs in trans. The active site, comprised of Cys144 and His41, is part of a chymotrypsin-like fold that is connected by a 16 residue loop to an extra domain featuring a novel alpha-helical fold. Molecular modelling and mutagenesis data implicate the loop in substrate binding and elucidate S1 and S2 subsites suitable to accommodate the side chains of the P1 glutamine and P2 leucine residues of M(pro) substrates. Interactions involving the N-terminus and the alpha-helical domain stabilize the loop in the orientation required for trans-cleavage activity. The study illustrates that RNA viruses have evolved unprecedented variations of the classical chymotrypsin fold.

Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain.,Anand K, Palm GJ, Mesters JR, Siddell SG, Ziebuhr J, Hilgenfeld R EMBO J. 2002 Jul 1;21(13):3213-24. PMID:12093723^[1]

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

References

↑ Anand K, Palm GJ, Mesters JR, Siddell SG, Ziebuhr J, Hilgenfeld R. Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain. EMBO J. 2002 Jul 1;21(13):3213-24. PMID:12093723 doi:10.1093/emboj/cdf327

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/1lvo"

@@ Line 1: / Line 1: @@
 ==Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain==
 <StructureSection load='1lvo' size='340' side='right' caption='[[1lvo]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1lvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lvo OCA], [http://pdbe.org/1lvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lvo RCSB], [http://www.ebi.ac.uk/pdbsum/1lvo PDBsum]</span></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=1lvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lvo OCA], [http://pdbe.org/1lvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lvo RCSB], [http://www.ebi.ac.uk/pdbsum/1lvo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lvo ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 29: @@
 </div>
 <div class="pdbe-citations 1lvo" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[RNA-directed RNA polymerase|RNA-directed RNA polymerase]]
 == References ==
 <references/>

1lvo

From Proteopedia

Revision as of 12:13, 12 October 2017

Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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