Molecular cloning demonstrates structural features of homologous bovine prohormone convertases 1 and 2

PC1 and PC2 (prohormone convertase) represent neuroendocrine members of the mammalian subtilisin-like family of proprotein convertases. The goal of th is study was to compare the primary sequence motifs of bovine PC1 and PC2 w ith those of homologs from other mammalian species to establish the structu ral basis for PC1 and PC2 activities in bovine that resemble other mammalia n homologs. Molecular cloning from bovine adrenal medulla resulted in the i solation of cDNAs for bovine PC1 and PC2 with highly conserved primary sequ ences with respect to signal sequence, prosegment, catalytic domain, and P domain. Bovine PC1 and PC2 contained the catalytic triad residues Asp, His, Ser, which are identical to the triads in PC1 and PC2 from other mammalian species. Bovine PC1 contained Asn as the oxyanion hole residue; in contras t, bovine PC2 contained Asp as the oxyanion hole residue, which is identica l to PC2 in other mammalian species. Bovine PC1 and PC2 possessed the P dom ain that contains the functional RRGDL motif, The cloned cDNAs detected exp ression of PC1 and PC2 mRNAs in bovine adrenal medulla, These results estab lish the defined structural domains of bovine PC1 and PC2 that are known to be essential for the activities of these enzymes in various species.