RESUMEN

The NMR structure is presented for compound 1 (BMS-480404) (Ki = 33 (+/-2) nM) bound to keratinocyte fatty acid-binding protein. This article describes interactions between a high affinity drug-like compound and a member of the fatty acid-binding protein family. A benzyl group ortho to the mandelic acid in 1 occupies an area of the protein that fatty acids do not normally contact. Similar to that in the kFABP-palmitic acid structure, the acid moiety in 1 is proximal to R129 and Y131. Computational modeling indicates that the acid moiety in 1 interacts indirectly via a modeled water molecule to R109.

Asunto(s)

Proteínas de Unión a Ácidos Grasos/antagonistas & inhibidores , Proteínas de Unión a Ácidos Grasos/química , Queratinocitos/metabolismo , Sitios de Unión , Simulación por Computador , Proteínas de Unión a Ácidos Grasos/metabolismo , Humanos , Ligandos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Molecular