Inhibitors of Fumarylacetoacetate Hydrolase Domain Containing Protein 1 (FAHD1).
Molecules
; 26(16)2021 Aug 18.
Article
en En
| MEDLINE
| ID: mdl-34443596
ABSTRACT
FAH domain containing protein 1 (FAHD1) acts as oxaloacetate decarboxylase in mitochondria, contributing to the regulation of the tricarboxylic acid cycle. Guided by a high-resolution X-ray structure of FAHD1 liganded by oxalate, the enzymatic mechanism of substrate processing is analyzed in detail. Taking the chemical features of the FAHD1 substrate oxaloacetate into account, the potential inhibitor structures are deduced. The synthesis of drug-like scaffolds afforded first-generation FAHD1-inhibitors with activities in the low micromolar IC50 range. The investigations disclosed structures competing with the substrate for binding to the metal cofactor, as well as scaffolds, which may have a novel binding mode to FAHD1.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Inhibidores Enzimáticos
/
Hidrolasas
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2021
Tipo del documento:
Article