Ontology highlight
ABSTRACT:
SUBMITTER: Joerger AC
PROVIDER: S-EPMC1635156 | biostudies-literature | 2006 Oct
REPOSITORIES: biostudies-literature
Joerger Andreas C AC Ang Hwee Ching HC Fersht Alan R AR
Proceedings of the National Academy of Sciences of the United States of America 20061002 41
The DNA-binding domain of the tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. We have solved high-resolution crystal structures of several oncogenic mutants to investigate the structural basis of inactivation and provide information for designing drugs that may rescue inactivated mutants. We found a variety of structural consequences upon mutation: (i) the removal of an essential contact with DNA, (ii) creation of large, water-accessible crevices or hydroph ...[more]