Structure of neprilysin in complex with the active metabolite of sacubitril.
Sci Rep
; 6: 27909, 2016 06 15.
Article
en En
| MEDLINE
| ID: mdl-27302413
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Compuestos de Bifenilo
/
Neprilisina
/
Aminobutiratos
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
Suiza