The hydrolysis of endothelins by neutral endopeptidase 24.11 (Enkephalinase)

J. Vijayaraghavan, A. G. Scicli, O. A. Carretero, Clive A. Slaughter, C. Moomaw, L. B. Hersh

Research output: Contribution to journalArticle

245 Citations (Scopus)

Abstract

Endothelins 1-3 are a family of 21-amino acid peptides whose structure consists of two rings formed by intra-chain disulfide bonds and a linear 'COOH-terminal tail'. These peptides were originally described on the basis of their potent vasoconstrictor activity. The hydrolytic inactivation of endothelin action has recently been implicated to be attributed, at least in part, to the enzyme neutral endopeptidase 24.11 (Scicli, A.G., Vijayaraghavan, Hersh, L., and Carretero, O. (1989) Hypertension 14, 353). The kinetic properties and mode of hydrolysis of the endothelins by this enzyme are reported in this study. The K(m) for endothelins 1 and 3 hydrolysis is approximately 2 μM while endothelin2 exhibits a 5-fold higher K(m). Endothelins 1 and 2 exhibit similar V(max) values while endothelin3 is hydrolyzed considerably more slowly. The initial cleavage site in endothelin1 is at the Ser5-Leu6 bond located within one of the cyclic structures. Thermolysin, a bacterial neutral endopeptidase with a similar substrate specificity to neutral endopeptidase 24.11 initially cleaves endothelin1 between His16-Leu17 which lies within the COOH-terminal linear 'tail' portion of the molecule. The cleavage of endothelins 2 and 3 by neutral endopeptidase 24.11 differs from that observed with endothelin1 in that cleavage of these endothelins occurs at Asp18-Ile19 within the linear COOH-terminal tail structure. These results demonstrate that the endothelins are good substrates for neutral endopeptidase 24.11 and suggest that their mode of cleavage is dependent upon both amino acid sequence as well as peptide conformation.

Original languageEnglish (US)
Pages (from-to)14150-14155
Number of pages6
JournalJournal of Biological Chemistry
Volume265
Issue number24
StatePublished - Sep 10 1990
Externally publishedYes

Fingerprint

Neprilysin
Endothelins
Hydrolysis
Endothelin-3
Endothelin-1
Endothelin-2
Peptides
Thermolysin
Amino Acids
Vasoconstrictor Agents
Substrates
Enzymes
Substrate Specificity
Disulfides
Conformations
Amino Acid Sequence
Hypertension
Molecules
Kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Vijayaraghavan, J., Scicli, A. G., Carretero, O. A., Slaughter, C. A., Moomaw, C., & Hersh, L. B. (1990). The hydrolysis of endothelins by neutral endopeptidase 24.11 (Enkephalinase). Journal of Biological Chemistry, 265(24), 14150-14155.

The hydrolysis of endothelins by neutral endopeptidase 24.11 (Enkephalinase). / Vijayaraghavan, J.; Scicli, A. G.; Carretero, O. A.; Slaughter, Clive A.; Moomaw, C.; Hersh, L. B.

In: Journal of Biological Chemistry, Vol. 265, No. 24, 10.09.1990, p. 14150-14155.

Research output: Contribution to journalArticle

Vijayaraghavan, J, Scicli, AG, Carretero, OA, Slaughter, CA, Moomaw, C & Hersh, LB 1990, 'The hydrolysis of endothelins by neutral endopeptidase 24.11 (Enkephalinase)', Journal of Biological Chemistry, vol. 265, no. 24, pp. 14150-14155.
Vijayaraghavan J, Scicli AG, Carretero OA, Slaughter CA, Moomaw C, Hersh LB. The hydrolysis of endothelins by neutral endopeptidase 24.11 (Enkephalinase). Journal of Biological Chemistry. 1990 Sep 10;265(24):14150-14155.
Vijayaraghavan, J. ; Scicli, A. G. ; Carretero, O. A. ; Slaughter, Clive A. ; Moomaw, C. ; Hersh, L. B. / The hydrolysis of endothelins by neutral endopeptidase 24.11 (Enkephalinase). In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 24. pp. 14150-14155.
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