Molecular abnormality of PI S variant of human alpha1-antitrypsin

Abstract

Alpha1-antitrypsin variant protein was purified to homogeneity from a PI S-S subject with a mild deficiency of plasma trypsin inhibiting capacity. Molecular weight, specific trypsin inhibitory activity, and composition of amino acids and carbohydrates were similar to the proteins purified from Pi M-M individuals with normal alpha1-antitrypsin activity. The structural difference between the normal and the variant alpha1-antitrypsin was elucidated by peptide mapping of their tryptic digests. An amino acid substitution of glutamic acid in the normal protein to valine in the variant protein was found. The result is consistent with the previously reported amino acid substitution in Pi S-Christchurch.