Title : Structural analysis of
neprilysin with various specific and potent inhibitors
Abstract :
- Neutral endopeptidase ( NEP ) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P , endothelin , bradykinin and atrial natriuretic factor
- Owing to the physiological importance of NEP in the modulation of nociceptive and pressor responses, there is considerable interest in inhibitors of this enzyme as novel analgesics and antihypertensive agents
- Here, the crystal structures of the soluble extracellular domain of human NEP ( residues 52-749 ) complexed with various potent and competitive inhibitors are described
- The structures unambiguously reveal the binding mode of the different zinc-chelating groups and the subsite specificity of the enzyme