2bip

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{{Seed}}
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{{STRUCTURE_2bip| PDB=2bip | SCENE= }}
{{STRUCTURE_2bip| PDB=2bip | SCENE= }}
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'''HUMAN P53 CORE DOMAIN MUTANT M133L-H168R-V203A-N239Y-R249S-N268D'''
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===HUMAN P53 CORE DOMAIN MUTANT M133L-H168R-V203A-N239Y-R249S-N268D===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15703170}}
==About this Structure==
==About this Structure==
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[[Category: Tumor suppressor]]
[[Category: Tumor suppressor]]
[[Category: Zinc]]
[[Category: Zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:20:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:17:33 2008''

Revision as of 11:17, 28 July 2008

Image:2bip.png

Template:STRUCTURE 2bip

HUMAN P53 CORE DOMAIN MUTANT M133L-H168R-V203A-N239Y-R249S-N268D

Template:ABSTRACT PUBMED 15703170

About this Structure

2BIP is a Single protein structure of sequence from Homo sapiens. 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

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