2bim
HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-R273H
OverviewOverview
We have solved the crystal structures of three oncogenic mutants of the core domain of the human tumor suppressor p53. The mutations were introduced into a stabilized variant. The cancer hot spot mutation R273H simply removes an arginine involved in DNA binding without causing structural distortions in neighboring residues. In contrast, the "structural" oncogenic mutations H168R and R249S induce substantial structural perturbation around the mutation site in the L2 and L3 loops, respectively. H168R is a specific intragenic suppressor mutation for R249S. When both cancer mutations are combined in the same molecule, Arg(168) mimics the role of Arg(249) in wild type, and the wild type conformation is largely restored in both loops. Our structural and biophysical data provide compelling evidence for the mechanism of rescue of mutant p53 by intragenic suppressor mutations and reveal features by which proteins can adapt to deleterious mutations.
About this StructureAbout this Structure
2BIM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structures of p53 cancer mutants and mechanism of rescue by second-site suppressor mutations., Joerger AC, Ang HC, Veprintsev DB, Blair CM, Fersht AR, J Biol Chem. 2005 Apr 22;280(16):16030-7. Epub 2005 Feb 9. PMID:15703170 Page seeded by OCA on Sat May 3 20:20:23 2008
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- Homo sapiens
- Single protein
- Fersht, A R.
- Joerger, A C.
- 3d-structure
- Activator
- Anti-oncogene
- Apoptosis
- Disease mutation
- Dna-binding
- Dna-binding protein
- Li-fraumeni syndrome
- Nuclear protein
- P53 dna-binding domain
- Phosphorylation
- Polymorphism
- Second-site suppressor mutation
- Superstable mutant
- Transcription regulation
- Transferase
- Tumor suppressor