Characterization of a proteinase inhibitor isolated from the fungal pathogen Coccidioides immitis.

A proteinase inhibitor was isolated from the cytosol and cell wall of the fungal respiratory pathogen Coccidioides immitis. The inhibitor was purified to apparent homogeneity by acid precipitation, gel filtration and reverse-phase h.p.l.c. It has an Mr of about 5000 under reducing conditions, as revealed by SDS/polyacrylamide-gel electrophoresis, and is both heat-stable and tolerant to low pH. The inhibitor can efficiently block activity of a 36,000-Mr serine proteinase previously isolated from the same cell-wall fraction of C. immitis, and the two molecules react in a 1:1 stoichiometry. The dissociation constant (Ki) of the enzyme-inhibitor complex is 2.3 x 10(-8) M. We suggest that the low-Mr inhibitor may play a role in regulation of the activity of the cell-wall-associated 36,000-Mr proteinase during sporulation of C. immitis.