2bim
From Proteopedia
| Line 5: | Line 5: | ||
==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== | ||
| - | 2BIM is a | + | 2BIM 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 and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BIM OCA]. |
==Reference== | ==Reference== | ||
| Line 36: | Line 36: | ||
[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:22:29 2007'' |
Revision as of 13:17, 5 November 2007
|
HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-R273H
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 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
2BIM is a Single protein structure of sequence from Homo sapiens with ZN and SO4 as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
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 Mon Nov 5 15:22:29 2007
Categories: Homo sapiens | Single protein | Fersht, A.R. | Joerger, A.C. | SO4 | 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 | Transferase | Tumor suppressor
