A new metallo- endopeptidase from human neuroblastoma NB-OK-1 cells which inactivates atrial natriuretic peptide by selective cleavage at the Ser123-Phe124 bond.
A novel metallo-endopeptidase from human neuroblastoma NB-OK-1 cells was partially purified and characterized. This enzyme activity was detected in the culture medium and could be detached from intact cells by gentle washing, suggesting a peripheral localization of the enzyme. This endopeptidase inactivated Atrial Natriuretic Peptide (ANP) by a unique and selective cleavage of the Ser123-Phe124 bond. It also produced hydrolysis at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bonds of other peptide hormones such as bradykinin, somatostatin 14, litorin, substance P, neuromedin C and angiotensin II. The substrate selectivity and inhibition profile of the enzyme showed obvious similarities with the peptide hormone inactivating endopeptidase (PHIE) recently purified from Xenopus laevis skin secretions and indicated a thermolysin-like activity distinct from neutral endopeptidase (EC 3.4.24.11) and from angiotensin converting enzyme (EC 3.4.15.1).
Delporte
C
C
Laboratoire de Chimie Biologique et de la Nutrition, l'Université Libre de Bruxelles, Belgique.
Carvalho
K M
KM
Leseney
A M
AM
Winand
J
J
Christophe
J
J
Cohen
P
P
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010649:Phenylalanine; D011480:Protease Inhibitors / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D012694:Serine; D014982:Xenopus laevis
D009479:Neuropeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D012694:Serine; D010649:Phenylalanine; D009320:Atrial Natriuretic Factor; D008666:Metalloendopeptidases