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2j20

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[[Image:2j20.gif|left|200px]]
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{{Seed}}
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[[Image:2j20.png|left|200px]]
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{{STRUCTURE_2j20| PDB=2j20 | SCENE= }}
{{STRUCTURE_2j20| PDB=2j20 | SCENE= }}
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'''HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-R273C'''
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===HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-R273C===
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==Overview==
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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 hydrophobic internal cavities with no other structural changes but with a large loss of thermodynamic stability, (iii) distortion of the DNA-binding surface, and (iv) alterations to surfaces not directly involved in DNA binding but involved in domain-domain interactions on binding as a tetramer. These findings explain differences in functional properties and associated phenotypes (e.g., temperature sensitivity). Some mutants have the potential of being rescued by a generic stabilizing drug. In addition, a mutation-induced crevice is a potential target site for a mutant-selective stabilizing drug.
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The line below this paragraph, {{ABSTRACT_PUBMED_17015838}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 17015838 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17015838}}
==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 Sun May 4 08:14:01 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:15:47 2008''

Revision as of 14:15, 28 July 2008

Image:2j20.png

Template:STRUCTURE 2j20

HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-R273C

Template:ABSTRACT PUBMED 17015838

About this Structure

2J20 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis for understanding oncogenic p53 mutations and designing rescue drugs., Joerger AC, Ang HC, Fersht AR, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15056-61. Epub 2006 Oct 2. PMID:17015838

Page seeded by OCA on Mon Jul 28 17:15:47 2008

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