Poliovirus thiol proteinase 3C can utilize a serine nucleophile within the putative catalytic triad.
The picornavirus 3C proteinases are substrate-specific thiol proteases that have been shown by secondary structure predictions and protein modeling studies to be similar to the trypsin-like serine proteases. We have examined several mutations of the 3C proteinase at putative active site and non-active site residues. The effect on 3C-mediated protein processing supports the model of serine protease similarity. In particular, we have shown that 3C can utilize a serine at position 147, which is predicted to supply the nucleophilic residue of the catalytic triad. We suggest that picornavirus 3C proteinases may represent a class of enzymes that have maintained the catalytic mechanism characteristic of a proposed enzyme ancestral to the highly divergent class of serine proteases.
Lawson
M A
MA
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92717.
Semler
B L
BL
D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D017955:Poliovirus / Q000201:enzymology* / Q000235:genetics; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012367:RNA, Viral / Q000235:genetics; D013462:Sulfur Radioisotopes; D014158:Transcription, Genetic
D004279:DNA, Viral; D012367:RNA, Viral; D013462:Sulfur Radioisotopes; D003546:Cysteine Endopeptidases