The proprotein convertases (PCs) are calcium-dependent proteases responsible for processing precursor proteins into their active forms in eukariotes. The PC1/3 is a pivotal enzyme of this family that participates in the proteolytic maturation of prohormones and neuropeptides inside the regulated secretory pathway. In this paper we demonstrate that mouse proprotein convertase 1/3 (mPC1/3) has a lag phase of activation by substrates that can be interpreted as a hysteretic behavior of the enzyme for their hydrolysis. This is an unprecedented observation in peptidases, but is frequent in regulatory enzymes with physiological relevance. The lag phase of mPC1/3 is dependent on substrate, calcium concentration and pH. This hysteretic behavior may have implications in the physiological processes in which PC1/3 participates and could be considered an additional control step in the peptide hormone maturation processes as for instance in the transformation of proinsulin to insulin. © 2011 Icimoto et al.
Icimoto, M. Y., Barros, N. M., Ferreira, J. C., Marcondes, M. F., Andrade, D., Machado, M. F., … Oliveira, V. (2011). Hysteretic behavior of proprotein convertase 1/3 (PC1/3). PLoS ONE, 6(9). https://doi.org/10.1371/journal.pone.0024545