Cathepsin B and other lysosomal cysteine proteinases are synthesized as inactive zymogens, which are converted to their mature forms by other proteases or by autocatalytic processing. Procathepsin B autoactivation was shown in vitro at pH 4.5 to be a bimolecular process with K(s) and k(cat) values of 2.1±0.9 μM and 0.12±0.02 s-1, respectively. Autoactivation is substantially accelerated in the presence of active cathepsin B molecules, indicating that mature cathepsin B is the catalytic species in the process. Proenzyme is cleaved without significant conformational changes as judged by circular dichroism, suggesting that propeptide unfolding occurs only after the cleavage. Procathepsin B autoactivation is pH-dependent with a pH optimum at 4.5 and with no processing observed at pH>6.0. However, in the presence of 0.5 μg/ml of dextran sulfate, relatively rapid processing is observed even at pH 6.5 (t(1/2)~90 min), suggesting that glycosaminoglycans are involved in in vivo processing of lysosomal cysteine proteases. Copyright (C) 1999 Federation of European Biochemical Societies.
Rozman, J., Stojan, J., Kuhelj, R., Turk, V., & Turk, B. (1999). Autocatalytic processing of recombinant human procathepsin B is a bimolecular process. FEBS Letters, 459(3), 358–362. https://doi.org/10.1016/S0014-5793(99)01302-2