title: Substitution of cysteine 192 in a highly conserved Streptococcus pyogenes extracellular cysteine protease (interleukin 1beta convertase) alters proteolytic activity and ablates zymogen processing.
abstract: Virtually all strains of the human pathogenic bacterium Streptococcus pyogenes express a highly conserved extracellular cysteine protease. The protein is made as an inactive zymogen of 40,000 Da and undergoes autocatalytic truncation to result in a 28,000-Da active protease. Numerous independent lines of investigation suggest that this enzyme participates in one or more phases of host-parasite interaction, such as inflammation and soft tissue invasion. Replacement of the single cysteine residue (C-192) with serine (C192S mutation) resulted in loss of detectable proteolytic activity against bovine casein, human fibronectin, and the low-molecular-weight synthetic substrate 7-amino-4-trifluoromethyl coumarin. The C192S mutant molecule does not undergo autocatalytic processing of zymogen to mature form. Taken together, these data support the hypothesis that C-192 participates in active-site formation and enzyme catalysis.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Musser
authors.forename: K
authors.initials: K
authors.lastname: Stockbauer
authors.forename: V
authors.initials: V
authors.lastname: Kapur
authors.forename: G W
authors.initials: GW
authors.lastname: Rudgers
mesh_terms: D000818:Animals; D001483:Base Sequence; D020170:Caspase 1; D002417:Cattle; D003545:Cysteine; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000502:physiology; D004792:Enzyme Precursors / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins / Q000096:biosynthesis; D013297:Streptococcus pyogenes / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D004792:Enzyme Precursors; D011994:Recombinant Proteins; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D003545:Cysteine