Crystal structure of peptide-bound neprilysin reveals key binding interactions.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "Crystal structure of peptide-bound neprilysin reveals key binding interactions."

Neprilysin (NEP) is a promiscuous zinc metalloprotease with a broad substrate specificity and cleaves a remarkable diversity of substrates through endopeptidase action. Two of these - amyloid-β and natriuretic peptides - implicate the enzyme in both Alzheimer's disease and cardiovascular disease, respectively. Here, we report the creation of a catalytically inactive NEP (E584D) to determine the first peptide-bound crystal structure at 2.6 Å resolution. The structure reveals key interactions involved in substrate binding which we have identified to be conserved in other known zinc metalloproteases. In addition, the structure provides evidence for a potential exosite within the central cavity that may play a critical role in substrate positioning. Together, these results contribute to our understanding of the molecular function of NEP.


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Name: FEBS letters
ISSN: 1873-3468


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