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Structures of soluble rabbit neprilysin complexed with phosphoramidon or thiorphan
Author(s) -
Labiuk Shaunivan L.,
Sygusch Jurgen,
Grochulski Pawel
Publication year - 2019
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x19006046
Subject(s) - phosphoramidon , neprilysin , thiorphan , chemistry , enkephalinase , extracellular , oligopeptide , endopeptidase , biophysics , biochemistry , pharmacology , enzyme , peptide , biology , receptor , enkephalin , opioid
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.