The neprilysin (NEP) family of zinc metalloendopeptidases: Genomics and function
Article first published online: 13 FEB 2001
Copyright © 2001 John Wiley & Sons, Inc.
Volume 23, Issue 3, pages 261–269, March 2001
How to Cite
Turner, A. J., Isaac, R. E. and Coates, D. (2001), The neprilysin (NEP) family of zinc metalloendopeptidases: Genomics and function. Bioessays, 23: 261–269. doi: 10.1002/1521-1878(200103)23:3<261::AID-BIES1036>3.0.CO;2-K
- Issue published online: 13 FEB 2001
- Article first published online: 13 FEB 2001
- The Biotechnology and Biological Sciences Research Council
- Medical Research Council
- British Heart Foundation
- the Leverhulme Trust
- the National Heart Research Fund
Neprilysin (NEP), a thermolysin-like zinc metalloendopeptidase, plays an important role in turning off peptide signalling events at the cell surface. It is involved in the metabolism of a number of regulatory peptides of the mammalian nervous, cardiovascular, inflammatory and immune systems. Examples include enkephalins, tachykinins, natriuretic and chemotactic peptides. NEP is an integral plasma membrane ectopeptidase of the M13 family of zinc peptidases. Other related mammalian NEP-like enzymes include the endothelin-converting enzymes (ECE-1 and ECE-2), KELL and PEX. A number of novel mammalian homologues of NEP have also recently been described. NEP family members are potential therapeutic targets, for example in cardiovascular and inflammatory disorders, and potent and selective inhibitors such as phosphoramidon have contributed to understanding enzyme function. Inhibitor design should be facilitated by the recent three-dimensional structural solution of the NEP–phosphoramidon complex. For several of the family members, however, a well-defined physiological function or substrate is lacking. Knowledge of the complete genomes of Caenorhabditis elegans and Drosophila melanogaster allows the full complement of NEP-like activities to be analysed in a single organism. These model organisms also provide convenient systems for examining cell-specific expression, developmental and functional roles of this peptidase family, and reveal the power of functional genomics. BioEssays 23:261–269, 2001. © 2001 John Wiley & Sons, Inc.