5JMY

NEPRILYSIN COMPLEXED WITH LBQ657

Summary for 5JMY

• Entry DOI: 10.2210/pdb5jmy/pdb
• Descriptor: Neprilysin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: hydrolase, lbq657, sacubitril, heart failure
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 162585.10

Authors

Schiering, N.,Wiesmann, C. (deposition date: 2016-04-29, release date: 2016-06-15, Last modification date: 2024-11-06)

Primary citation

Schiering, N.,D'Arcy, A.,Villard, F.,Ramage, P.,Logel, C.,Cumin, F.,Ksander, G.M.,Wiesmann, C.,Karki, R.G.,Mogi, M.
Structure of neprilysin in complex with the active metabolite of sacubitril.
Sci Rep, 6:27909-27909, 2016

PubMed Abstract: Sacubitril is an ethyl ester prodrug of LBQ657, the active neprilysin (NEP) inhibitor, and a component of LCZ696 (sacubitril/valsartan). We report herein the three-dimensional structure of LBQ657 in complex with human NEP at 2 Å resolution. The crystal structure unravels the binding mode of the compound occupying the S1, S1' and S2' sub-pockets of the active site, consistent with a competitive inhibition mode. An induced fit conformational change upon binding of the P1'-biphenyl moiety of the inhibitor suggests an explanation for its selectivity against structurally homologous zinc metallopeptidases.

PubMed: 27302413
DOI: 10.1038/srep27909

Experimental method

X-RAY DIFFRACTION (2 Å)