research communications
Neutral endopeptidase (neprilysin; NEP) is a proteinase that cleaves a wide variety of peptides and has been implicated in Alzheimer's disease, cardiovascular conditions, arthritis and other inflammatory diseases. The structure of the soluble extracellular domain (residues 55–750) of rabbit neprilysin was solved both in its native form at 2.1 Å resolution, and bound to the inhibitors phosphoramidon and thiorphan at 2.8 and 3.0 Å resolution, respectively. Consistent with the extracellular domain of human neprilysin, the structure reveals a large central cavity which contains the active site and the location for inhibitor binding.
Supporting information
PDB references: soluble rabbit neprilysin, 4xbh; complex with phosphoramidon, 4zr5; complex with thiorphan, 5v48