RESUMEN

The X-ray crystal structure of the src SH2 domain revealed the presence of a thiol residue (Cys 188) located proximal to the phosphotyrosine portion of a dipeptide ligand. An aldehyde bearing ligand (1) was designed to position an electrophilic carbonyl group in the vicinity of the thiol. X-ray crystallographic and NMR examination of the complex formed between (1) and the src SH2 domain revealed a hemithioacetal formed by addition of the thiol to the aldehyde group with an additional stabilizing hydrogen bond between the acetal hydroxyl and a backbone carbonyl.

Asunto(s)

Dipéptidos/química , Conformación Proteica , Proteínas/química , Dominios Homologos src , Aldehídos , Secuencia de Aminoácidos , Sitios de Unión , Cristalografía por Rayos X , Cisteína , Dipéptidos/síntesis química , Enlace de Hidrógeno , Ligandos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Fosfotirosina