title: Autocatalytic activation of C1r subcomponent of the first component of human complement.
abstract: Autoactivation of the proenzyme form of a subunit of the first component (C1r) was performed in the presence and absence of diisopropyl fluorophosphate (DFP). The time-course of autoactivation of zymogen C1r followed a sigmoidal curve and was accelerated by addition of the enzyme C1r and by increasing the concentration of C1r, suggesting that autoactivation of C1r consists of two intermolecular reactions, i.e. zymogen(C1r)- and enzyme(C1r)-catalyzed reactions. In the presence of 10 mM DFP, the enzyme-catalyzed autoactivation of C1r was completely inhibited, while the zymogen-catalyzed autoactivation still proceeded depending upon C1r concentration. These results suggested that the zymogen-catalyzed autoactivation of C1r is a DFP-insensitive second-order reaction and is mediated by an active site generated in a single chain C1r through a conformational change (Kassahara et al. (1982) FEBS lett. 141, 128-131). Based on these results, a possible reaction process of autoactivation of C1r was proposed, as follows: (formula; see text) where C1r represents a conformational isomer which catalyzes the autoactivation of C1r, and the rate constants, k2 and k3, are of second-order. Utilizing a computer, we simulated the autoactivation of C1r and found the above scheme to be a reasonable model of C1r autoactivation. Evidence which supports the formation of a conformational isomer of C1r, C1r, as an intermediate in its autoactivation was also obtained by a surface radiolabeling method.
authors.forename: Y
authors.initials: Y
authors.lastname: Kasahara
authors.forename: H
authors.initials: H
authors.lastname: Odai
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Nagasawa
authors.forename: J
authors.initials: J
authors.lastname: Koyama
mesh_terms: D003166:Complement Activating Enzymes / Q000378:metabolism*; D015923:Complement C1r; D003201:Computers; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D007536:Isomerism; D007700:Kinetics; D011487:Protein Conformation
chemical_list: D007531:Isoflurophate; D003166:Complement Activating Enzymes; D015923:Complement C1r