title: Degradation of lysylbradykinin by endopeptidase 24.11 and endopeptidase 24.15.
abstract: Lysylbradykinin (LBK), a potent bioactive peptide with pleiotropic actions, is the major kinin generated in the extravascular space. To explore possible mechanisms of inactivation of this peptide in tissues, we evaluated its degradation by endopeptidase 24.11 (EP 24.11) and endopeptidase 24.15 (EP 24.15), two zinc metalloenzymes widely distributed in tissues. EP 24.11 cleaved LBK at the Gly5-Phe6 and Pro8-Phe9 bonds, whereas EP 24.15 cleaved the Phe6-Ser7 bond. Determination of kinetic constants for degradation of LBK by the two enzymes yielded kcat/Km ratios of 5.2 x 10(5) and 8.4 x 10(5) for EP 24.15 and EP 24.11, respectively, indicating that LBK is a good substrate for both enzymes. The findings demonstrate that both EP 24.11 and EP 24.15 efficiently degrade LBK and thus may contribute to the inactivation of this peptide in tissues.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rosenbaum
authors.forename: C
authors.initials: C
authors.lastname: Cardozo
authors.forename: M
authors.initials: M
authors.lastname: Lesser
mesh_terms: D000595:Amino Acid Sequence; D007609:Kallidin / Q000378:metabolism*; D007700:Kinetics; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015260:Neprilysin / Q000378:metabolism*
chemical_list: D007609:Kallidin; D008666:Metalloendopeptidases; D015260:Neprilysin; C022510:thimet oligopeptidase