Procongopain from Trypanosoma congolense is processed at basic pH: an unusual feature among cathepsin L-like cysteine proteases.
Congopain, the major cysteine protease from Trypanosoma congolense, is synthesized as an inactive zymogen, and further converted into its active form after removal of the proregion, most probably via an autocatalytic mechanism. Processing of recombinant procongopain occurs via an apparent one-step or a multistep mechanism depending on the ionic strength. The auto-activation is pH-dependent, with an optimum at pH 4.0, and no activation observed at pH 6.0. After addition of dextran sulfate (10 microg/ml), an approx. 20-fold increase of processing (expressed as enzymatic activity) is observed. Furthermore, in the presence of dextran sulfate, procongopain can be processed at pH 8.0, an unusual feature among papain-like enzymes. Detection of procongopain and trypanosomal enzymatic activity in the plasma of T. congolense-infected cattle, together with the capacity of procongopain to be activated at weakly basic pH, suggest that procongopain may be extracellularly processed in the presence of blood vessel glycosaminoglycans, supporting the hypothesis that congopain acts as a pathogenic factor in host-parasite relationships.
Serveau
Carole
C
Protéases et Vectorisation, INSERM EMI-U 00.10, Laboratoire d'Enzymologie et Chimie des Protéines, Faculté de Médecine, Université François Rabelais, F-37032 Tours, France.
Boulangé
Alain
A
Lecaille
Fabien
F
Gauthier
Francis
F
Authié
Edith
E
Lalmanach
Gilles
G
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002417:Cattle / Q000469:parasitology*; D003546:Cysteine Endopeptidases / Q000097:blood / Q000378:metabolism*; D016264:Dextran Sulfate / Q000494:pharmacology; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000097:blood / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014348:Trypanosoma congolense / Q000201:enzymology*
D004792:Enzyme Precursors; D016264:Dextran Sulfate; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C084086:congopain; D056668:Cathepsin L