title: Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases.
abstract: The picornavirus family includes several pathogens such as poliovirus, rhinovirus (the major cause of the common cold), hepatitis A virus and the foot-and-mouth disease virus. Picornaviral proteins are expressed by direct translation of the genomic RNA into a single, large polyprotein precursor. Proteolysis of the viral polyprotein into the mature proteins is assured by the viral 3C enzymes, which are cysteine proteinases. Here we report the X-ray crystal structure at 2.3 A resolution of the 3C proteinase from hepatitis A virus (HAV-3C). The overall architecture of HAV-3C reveals a fold resembling that of the chymotrypsin family of serine proteinases, which is consistent with earlier predictions. Catalytic residues include Cys 172 as nucleophile and His 44 as general base. The 3C cleavage specificity for glutamine residues is defined primarily by His 191. The overall structure suggests that an intermolecular (trans) cleavage releases 3C and that there is an active proteinase in the polyprotein.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Allaire
authors.forename: M M
authors.initials: MM
authors.lastname: Chernaia
authors.forename: B A
authors.initials: BA
authors.lastname: Malcolm
authors.forename: M N
authors.initials: MN
authors.lastname: James
mesh_terms: D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D002918:Chymotrypsin / Q000737:chemistry; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics; D006507:Hepatovirus / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D014764:Viral Proteins; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases