Atriopeptin III degradation by endopeptidase 24.11: the Cys-Phe bond is not the preferential cleavage site.
Incubation of rANP(5-28)--also called atriopeptin III (AP III)--with purified endopeptidase 24.11 led preferentially to the production of Phe-Arg-Tyr, while other products of minor importance were detected. One of these was identified as rANP(5-25) (atriopeptin I) (AP I). This hydrolysis pattern of endopeptidase 24.11 towards AP III differs from the known favored site of cleavage at the Cys7-Phe8 bond of rANP(1-28). Moreover, by comparison with rANP(1-28), the degradation rate of AP III was slower. These data suggest that N-terminal peptide truncation results in conformational and/or charge modifications leading to a different positioning of the peptide in the endopeptidase 24.11 active site. In most hypothalamic nuclei of the rat brain known to contain AP III and endopeptidase 24.11, the preferential Ser25-Phe26 bond hydrolysis, although supposed to be responsible for a reduced degradation rate, might represent an effective enzymatic pathway of catabolism for AP III.
Nortier
J
J
Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomédicale, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Pauwels
S
S
De Prez
E
E
Deschodt-Lanckman
M
M
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments; D051381:Rats
D009842:Oligopeptides; D010446:Peptide Fragments; C472610:atrial natriuretic peptide, rat; C062525:atrial natriuretic factor prohormone (103-126); D009320:Atrial Natriuretic Factor; D015260:Neprilysin