6sh2

Publication Abstract from PubMed

Neprilysin (NEP) is a promiscuous zinc metalloprotease with broad substrate specificity and cleaves a remarkable diversity of substrates through endopeptidase action. Two of these - amyloid-beta 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 A 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.

Crystal structure of peptide-bound neprilysin reveals key binding interactions.,Moss S, Subramanian V, Acharya KR FEBS Lett. 2020 Jan;594(2):327-336. doi: 10.1002/1873-3468.13602. Epub 2019 Sep, 21. PMID:31514225^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.