Purification and characterization of a metacestode cysteine proteinase fromTaenia soliuminvolved in the breakdown of human IgG

Abstract

Infection of the central nervous system byTaenia soliumcysticerci is the cause of human neurocysticercosis, a major neurological infection in the Third World and an emerging infectious disease in the United States. We previously isolated a cysteine proteinase from cysticerci ofTaenia crassicepsand demonstrated that it degrades human IgGin vitro. We have now isolated a 48 kDa thiol-dependent proteinase fromT. solium. TheT. soliumenzyme also degrades human IgG, but does not significantly degrade albumin. IgG degradation was inhibited by cysteine proteinase inhibitors, but not significantly by inhibitors of aspartic, serine, or metalloproteinases. The peptide substrate specificity and pH optimum resemble cathepsin L. The Km for the peptide substrate Z-Phe-Arg-AFC was calculated to be 7·0×10⁻⁶M, the Kcat was 1·98×10⁵s⁻¹, and the Kcat/Km 2·84×10⁹M⁻¹s⁻¹, a value which is within the diffusion control limit for highly catalytic enzymes. We propose that immunoglobulin degradation by theT. soliumcysteine proteinase may play a key role in the host-parasite interface and could be employed as a target for chemotherapy.