5jmy
From Proteopedia
NEPRILYSIN COMPLEXED WITH LBQ657
Structural highlights
FunctionNEP_HUMAN Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers.[1] [2] [3] Publication Abstract from PubMedSacubitril 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 A 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. Structure of neprilysin in complex with the active metabolite of sacubitril.,Schiering N, D'Arcy A, Villard F, Ramage P, Logel C, Cumin F, Ksander GM, Wiesmann C, Karki RG, Mogi M Sci Rep. 2016 Jun 15;6:27909. doi: 10.1038/srep27909. PMID:27302413[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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