NRD CONVERTASE AND AMINOPEPTIDASE-B - 2 PROCESSING METALLOPEPTIDASES WITH A SELECTIVITY FOR BASIC RESIDUES

An endoprotease and an aminopeptidase B were isolated from rat testis and characterized, The first one is a metalloendopeptidase of 1161 res idues which contains a canonical HXXEHX76E Zn-2+-binding site and an a cidic stretch of 71 amino acids containing 79 % of Glu and Asp, It exh ibits an in vitro selectivity for peptide bonds at the N-terminus of A rg (R) moieties in dibasic sites and was thus called NRD convertase (N ardilysin: EC 3.4.24.61), It belongs to the pitrilysin family and show s 24 and 34 % identity with E. coli protease III (EC 3.4.24.54) and in sulysin (EC 3.4.24.55) respectively. The aminopeptidase B component is a 72 kDa metalloexopeptidase which is able to remove Lys and Arg resi dues from naphtylamide derivatives and from the N-terminus of various peptide substrates, A combination of biochemical and immunochemical st udies revealed its ubiquitous character. In the testis, both enzymes a re highly expressed at late stages of spermatogenesis and NRD converta se expression is exclusively restricted to the germ cells, The subcell ular localization of both enzymes supports the involvement of aminopep tidase B in processing events associated with the secretory pathway bu t led to new hypothesis on the possible physiological role(s) of NRD c onvertase.