INVESTIGADORES
APPIGNANESI Gustavo Adrian
artículos
Título:
Wrapping Effects within a Proposed Function-Rescue Strategy for the Y220C Oncogenic Mutation of Protein p53
Autor/es:
S. ACCORDINO; J. A. RODRÍGUEZ FIRS; G. A. APPIGNANESI
Revista:
PLOS ONE
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2013 vol. 8 p. 55123 - 55133
ISSN:
1932-6203
Resumen:
Soluble proteins must protect their structural integrity from water attack by wrapping interactions which imply the
clustering of nonpolar residues around the backbone hydrogen bonds. Thus, poorly wrapped hydrogen bonds constitute
defects which have been identified as promoters of protein associations since they favor the removal of hydrating
molecules. More specifically, a recent study of our group has shown that wrapping interactions allow the successful
identification of protein binding hot spots. Additionally, we have also shown that drugs disruptive of protein-protein
interfaces tend to mimic the wrapping behavior of the protein they replace. Within this context, in this work we study
wrapping three body interactions related to the oncogenic Y220C mutation of the tumor suppressor protein p53. Our
computational results rationalize the oncogenic nature of the Y220C mutation, explain the binding of a drug-like molecule
already designed to restore the function of p53 and provide clues to help improve this function-rescue strategy and to
apply in other drug design or re-engineering techniques.