title: Hysteretic behavior of proprotein convertase 1/3 (PC1/3).
abstract: 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.
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Marcelo Y
authors.initials: MY
authors.lastname: Icimoto
authors.forename: Nilana M
authors.initials: NM
authors.lastname: Barros
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Ferreira
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Marcondes
authors.forename: Douglas
authors.initials: D
authors.lastname: Andrade
authors.forename: Mauricio F
authors.initials: MF
authors.lastname: Machado
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.forename: Wagner A
authors.initials: WA
authors.lastname: Júdice
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.forename: Vitor
authors.initials: V
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D054808:Histatins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D051379:Mice; D045664:Proprotein Convertase 1 / Q000378:metabolism*
chemical_list: C068075:HTN3 protein, human; D054808:Histatins; D045664:Proprotein Convertase 1; D002118:Calcium