Expression of Multiple Genes for Pregnancy-Associated Glycoproteins in the Sheep Placenta

Abstract

Bovine pregnancy-associated glycoprotein l(boPAGl) (1), also known as pregnancy-specific protein B (2), was initially identified as a unique placental antigen in cattle by raising antisera against total placental proteins in rabbits. Serologically similar antigens have also been found in sheep and other ruminant ungulates (3). Subsequently, molecular cloning showed that bo- and ovine (ov) PAG1 belong to the superfamily of aspartic proteinases (4). Unlike other known aspartic proteinases, however, both bo- and ovPAGl appear to be enzymatically inactive due to key mutations around the catalytic site regions (4,5). For instance, the catalytic aspartic acid residue in the C-terminal lobe of ovPAGl is mutated to glycine. A similar mutation in the N-terminal lobe of porcine pepsin completely inactivates the molecule (6). By analogy, it seems unlikely that ovPAGl could function as a proteinase. BoPAGl, despite retaining both active site aspartic acid residues, has a mutation within the N-terminal D—T—G triad, in which the highly conserved glycine is replaced by an alanine. It is hypothesized that the methyl group of the alanine would displace the catalytic water molecule from its normal position between the two catalytic aspartic acid residues (4,7), thereby impairing the activity of the molecule. In addition, other critical alterations around the substrate binding pockets are likely to disfavor the potential of both PAG1 as active proteinases (7).