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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'''
| | ===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. | | The line below this paragraph, {{ABSTRACT_PUBMED_17015838}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17015838 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17015838}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Tumor suppressor]] | | [[Category: Tumor suppressor]] |
| [[Category: Zinc]] | | [[Category: Zinc]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 08:14:01 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:15:47 2008'' |