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Acta Crystallogr D Biol Crystallogr. 2004 Feb;60(Pt 2):392-6. Epub 2004 Jan 23.

Structural analysis of neprilysin with various specific and potent inhibitors.

Author information

1
Morphochem AG, CH-4058 Basel, Switzerland.

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.

PMID:
14747736
DOI:
10.1107/S0907444903027410
[Indexed for MEDLINE]

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