Nardilysin cleaves peptides at monobasic sites

K. Martin Chow, Oliver Oakley, Jack Goodman, Zhangliang Ma, Maria Aparecida Juliano, Luiz Juliano, Louis B. Hersh

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Nardilysin (N-arginine dibasic convertase, EC was first identified on the basis of its ability to cleave peptides containing an arginine dibasic pair, i.e., Arg-Arg or Arg-Lys. However, it was observed that an aromatic residue adjacent to the dibasic pair (i.e., Phe-Arg-Lys) could alter the cleavage site. In this study we determined whether nardilysin can cleave peptides at a single basic residue. Nardilysin cleaves β-endorphin at the monobasic site, Phe17-Lys18, with a kcat/Km of 2 × 108 M-1 min-1. This can be compared to a kcat/Km of 8.5 × 108 M-1 min-1 for cleavage between a dibasic pair in dynorphin B-13. Nardilysin also cleaves calcitonin at His-Arg and somatostatin-14 at Cys-Lys. We examined the hydrolysis of fluorogenic peptides based on the β-endorphin 12-24 sequence, Abz-T-P-L-V-T-L-X1-X2-N-A-I-I-K-Q-EDDnp. Nardilysin hydrolyzes the peptides when X1-X2 = F-K, F-R, W-K, M-K, Y-K, and L-K. The kinetics of cleavage at F-K and F-R are similar; however, K-F is not hydrolyzed. Nardilysin cleaves at two monobasic sites M-K and F-R of the kallidin model peptide Abz-MISLMKRPPGFSPFRSSRI-NH2, releasing desArg10 kallidin (KRPPGFSPF). However, nardilysin does not release desArg10 kallidin from the physiological precursor low molecular weight kininogen. These studies extend the range of potential substrates for nardilysin and further substantiate that nardilysin is a true peptidase.

Original languageEnglish
Pages (from-to)2239-2244
Number of pages6
Issue number7
StatePublished - Feb 25 2003

ASJC Scopus subject areas

  • Biochemistry


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