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Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases

Nature volume 369, pages 72–76 (1994)Cite this article

Abstract

THE picornavirus family includes several pathogens such as poliovirus, rhinovirus (the major cause of the common cold), hepat-itis 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 precursor1,2. Proteolysis of the viral polyprotein into the mature proteins is assured by the viral 3C enzymes, which are cysteine proteinases3–6. Here we report the X-ray crystal structure at 2.3 Å 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 predictions7,8. Cata-lytic 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 inter-molecular (trans) cleavage releases 3C and that there is an active proteinase in the polyprotein.

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Author notes

  1. Bruce A. Malcolm and Michael N. G. James: Department of Biochemistry and Department of Medical Microbiology and Infectious Diseases, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

Affiliations

  1. MRC Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada

    Marc Allaire, Maia M. Chernaia, Bruce A. Malcolm & Michael N. G. James

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  1. Marc Allaire
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  2. Maia M. Chernaia
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  3. Bruce A. Malcolm
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  4. Michael N. G. James
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Allaire, M., Chernaia, M., Malcolm, B. et al. Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases. Nature 369, 72–76 (1994). https://doi.org/10.1038/369072a0

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