title: Rapid inhibition of the sperm protease acrosin by protein C inhibitor.
abstract: Heparin was found to be an allosteric modulator of the amidolytic activity of the protease acrosin. In the presence of saturating concentrations of heparin, there was a 4.9-fold decrease in the value of the Michaelis constant for the substrate D-Ile-Pro-Arg-p-nitroanilide and the value of kcat was 2.5-fold lower. Analysis of the data yielded a dissociation constant of 0.22 +/- 0.04 microM for the heparin-acrosin complex. The presence of relatively high concentrations of protein C inhibitor in seminal plasma [Laurell, M., Christensson, A., Abrahamson, P., Stenflo, J., & Lilja, H. (1992) J. Clin. Invest. 89, 1094-1101] suggests that this serpin may be involved in the control of the activity of acrosin. Acrosin was found to be rapidly inhibited by protein C inhibitor with the association rate constant (kass) for the formation of the complex being (2.41 +/- 0.03) x 10(5) M-1 s-1. The value of kass showed a bell-shaped dependence on the concentration of heparin; it was maximal at concentrations of heparin between 0.08 and 3 microM and decreased at lower and higher concentrations. At the optimal heparin concentration, the value of kass for the acrosin-protein C inhibitor reaction was 230-fold higher ((5.6 +/- 0.1) x 10(7) M-1 s-1) than in the absence of heparin. The results suggest that protein C inhibitor may be important in the physiological control of acrosin activity, particularly where the presence of heparin-like glycosaminoglycans would stimulate the acrosin-protein C inhibitor reaction.
authors.affiliation: Department of Haematology, University of Cambridge, U.K.
authors.forename: J M
authors.initials: JM
authors.lastname: Hermans
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: S R
authors.initials: SR
authors.lastname: Stone
mesh_terms: D000176:Acrosin / Q000037:antagonists & inhibitors*; D000595:Amino Acid Sequence; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D018046:Protein C Inhibitor / Q000494:pharmacology*; D013094:Spermatozoa / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D009842:Oligopeptides; D018046:Protein C Inhibitor; D006493:Heparin; D000176:Acrosin