2bio: Difference between revisions
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==Overview== | ==Overview== | ||
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 . | 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 Structure== | ==About this Structure== | ||
2BIO is a | 2BIO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BIO OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
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Revision as of 16:15, 5 November 2007
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HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-R249S-N268D
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
2BIO is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Structure known Active Site: AC1. 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
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Fersht, A.R.
- Joerger, A.C.
- ZN
- 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
- Tumor suppressor