NRD convertase and aminopeptidase B: two 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 residues which contains a canonical HXXEHX76E Zn(2+)-binding site and an acidic stretch of 71 amino acids containing 79% of Glu and Asp. It exhibits an in vitro selectivity for peptide bonds at the N-terminus of Arg (R) moieties in dibasic sites and was thus called NRD convertase (Nardilysin: EC 3.4.24.61). It belongs to the pitrilysin family and shows 24 and 34% identity with E. coli protease III (EC 3.4.24.54) and insulysin (EC 3.4.24.55) respectively. The aminopeptidase B component is a 72 kDa metalloexopeptidase which is able to remove Lys and Arg residues from naphtylamide derivatives and from the N-terminus of various peptide substrates. A combination of biochemical and immunochemical studies revealed its ubiquitous character. In the testis, both enzymes are highly expressed at late stages of spermatogenesis and NRD convertase expression is exclusively restricted to the germ cells. The subcellular localization of both enzymes supports the involvement of aminopeptidase B in processing events associated with the secretory pathway but led to new hypothesis on the possible physiological role(s) of NRD convertase.
Laboratoire de Biochimie des Signaux Régulateurs Cellulaires et Moléculaires, Université Pierre et Marie-Curie, Paris, France.
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Foulon
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Cadel
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Prat
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Chesneau
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Hospital
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Segrétain
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Cohen
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002413:Cations, Divalent / Q000494:pharmacology; D006639:Histidine / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D051381:Rats; D013004:Somatostatin / Q000378:metabolism; D013091:Spermatogenesis; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology*
D002413:Cations, Divalent; D006639:Histidine; D013004:Somatostatin; D001120:Arginine; D000626:Aminopeptidases; C019721:aminopeptidase B; D008666:Metalloendopeptidases; C087976:nardilysin