Structural characterization of BRCT-tetrapeptide binding interactions.
Biochem Biophys Res Commun
; 393(2): 207-10, 2010 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-20122900
ABSTRACT
BRCT(BRCA1) plays a major role in DNA repair pathway, and does so by recognizing the conserved sequence pSXXF in its target proteins. Remarkably, tetrapeptides containing pSXXF motif bind with high specificity and micromolar affinity. Here, we have characterized the binding interactions of pSXXF tetrapeptides using NMR spectroscopy and calorimetry. We show that BRCT is dynamic and becomes structured on binding, that pSer and Phe residues dictate overall binding, and that the binding affinities of the tetrapeptides are intimately linked to structural and dynamic changes both in the BRCT(BRCA1) and tetrapeptides. These results provide critical insights for designing high-affinity BRCT(BRCA1) inhibitors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Desenho de Fármacos
/
Proteína BRCA1
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article