2j1x

From Proteopedia

Revision as of 15:17, 30 October 2007

HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-Y220C-N239Y-N268D

Overview

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 ... [(full description)]

About this Structure

2J1X 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].

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

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