N-ARGININE DIBASIC CONVERTASE, A METALLOENDOPEPTIDASE AS A PROTOTYPE OF A CLASS OF PROCESSING ENZYMES

N-Arg dibasic convertase rsa metalloendopeptidase from rat brain corte x and testis that cleaves peptide substrates on the N terminus of Arg residues in dibasic stretches. By using both an oligonucleotide and an tibodies to screen a rat testis cDNA library, a full-length cDNA was i solated. The sequence contains an open reading frame of 1161 codons co rresponding to a protein of 133 kDa that exhibits 35% and 48% similari ty with Escherichia coli protease III (pitrilysin, EC 3.4.99.44) and r at or human insulinase (EC 3.4.99.45), respectively. Moreover, the pre sence of the HXXEH amino acid signature (XX = FL) clearly classifies N -Arg dibasic convertase as a member of the pitrilysin family of zinc-m etalloendopeptidases. In addition, a Cys residue that may be responsib le for the thiol sensitivity of the insulinase and N-Arg dibasic conve rtase was proposed. The protein sequence contains a distinctive additi onal feature consisting of a stretch of 71 acidic amino acids. We hypo thesize that this metalloendopeptidase may be a member of a distinct c lass of processing enzymes.