MOLECULAR CHARACTERIZATION OF HUMAN AND BOVINE ENDOTHELIN-CONVERTING ENZYME (ECE-1)

A membrane-bound protease activity that specifically converts Big endo thelin-1 has been purified from bovine endothelial cells (FBHE). The e nzyme was cleaved with trypsin and the peptide sequencing analysis con firmed it to be a zinc chelating metalloprotease containing the typica l HEXXH (HELTH) motif. RT-PCR and cDNA screens were employed to isolat e the complete cDNAs of the bovine and human enzymes. This human metal loprotease was expressed heterologously in cell culture and oocytes. T he catalytic activity of the recombinant enzyme is the same as that de termined for the natural enzyme. The data suggest that the characteriz ed enzyme represents the functional human endothelin converting enzyme ECE-1.