Open AccessPepsin-inhibitory activity of the uterine serpins
Author(s) -
Nagappan Mathialagan,
Thomas Hansen
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.24.13653
Subject(s) - serpin , pepstatin , serine proteinase inhibitors , biochemistry , biology , serine , glycoprotein , peptide sequence , amino acid , pepsin , microbiology and biotechnology , protease , serine protease , enzyme , gene
Among the major products secreted by the uteri of cattle, sheep, and pigs during pregnancy are glycoproteins with amino acid sequences that place them in the serpin (ser inep roteinasein hibitor) superfamily of proteins. The inferred amino acid sequences for bovine uterine serpin (boUS-1) and ovine uterine serpin (ovUS-1) exhibit about 72% sequence identity to each other but only about 50% and 56% identity, respectively, to two distinct porcine uterine serpins (poUS-1 and poUS-2). Despite these differences in primary structure, the uterine serpins possess well-conserved reactive center loop regions that contain several motifs present in the propeptide regions of pepsinogens. One such motif, VVVK, aligns with the first 4 amino acids of the aspartic proteinase inhibitor pepstatin. Although no inhibitory activity toward any serine proteinase has been found, at least one of the uterine serpins, ovUS-1, can bind specifically to immobilized pepsin A and can weakly inhibit the proteolytic activities of pepsin A and C (but not cathepsins D and E). OvUS-1 is the first specific inhibitor of aspartic proteinases to be identified in vertebrates and provides another example of a serpin with “crossover” activity. The pregnancy-associated glycoproteins (PAGs), which are secreted by the trophoblast layer of the placentas of ungulate species and are inactive members of the aspartic proteinase family, can also bind ovUS-1 and may be the natural target partners for the uterine serpins.