Solution conformation of an essential region of the p53 transactivation domain.
Fold Des
; 2(6): 331-42, 1997.
Article
en En
| MEDLINE
| ID: mdl-9427007
BACKGROUND: The peptide segment surrounding residues Leu22 and Trp23 of the p53 transactivation domain plays a critical role in the transactivation activity of p53. This region binds basal transcriptional components such as the TATA-box binding protein associated factors TAFII40 and TAFII60 as well as the mdm-2 and adenovirus type 5 E1B 55 kDa oncoproteins. RESULTS: The structure of residues 14-28 of p53 was studied by nuclear magnetic resonance spectroscopy and found to prefer a two-beta-turn structure stabilized by a hydrophobic cluster consisting of residues known to be important for transactivation and binding to p53-binding proteins. A peptide segment in which Leu22 and Trp23 were replaced by Gln and Ser displays a random structure. CONCLUSIONS: This structural propensity observed in the wild-type p53 peptide is important for understanding the mechanism of transcriptional activation, because very few structural data are available on transactivation domains to date. These results should aid in the design of therapeutics that could competitively inhibit binding of p53 to the oncogene product mdm-2.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Conformación Proteica
/
Transactivadores
/
Proteína p53 Supresora de Tumor
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Fold Des
Asunto de la revista:
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido