2ioo: Difference between revisions
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'''Crystal structure of the mouse p53 core domain''' | {{Structure | ||
|PDB= 2ioo |SIZE=350|CAPTION= <scene name='initialview01'>2ioo</scene>, resolution 2.02Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | |||
|ACTIVITY= | |||
|GENE= Tp53, P53, Trp53 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]) | |||
}} | |||
'''Crystal structure of the mouse p53 core domain''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
2IOO is a [ | 2IOO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IOO OCA]. | ||
==Reference== | ==Reference== | ||
High-resolution structure of the p53 core domain: implications for binding small-molecule stabilizing compounds., Ho WC, Luo C, Zhao K, Chai X, Fitzgerald MX, Marmorstein R, Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1484-93. Epub 2006, Nov 23. PMID:[http:// | High-resolution structure of the p53 core domain: implications for binding small-molecule stabilizing compounds., Ho WC, Luo C, Zhao K, Chai X, Fitzgerald MX, Marmorstein R, Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1484-93. Epub 2006, Nov 23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17139084 17139084] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: ig fold]] | [[Category: ig fold]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:31:52 2008'' | ||
Revision as of 18:31, 20 March 2008
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| , resolution 2.02Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | Tp53, P53, Trp53 (Mus musculus) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the mouse p53 core domain
OverviewOverview
The p53 transcriptional regulator is the most frequently mutated protein in human cancers and the majority of tumor-derived p53 mutations map to the central DNA-binding core domain, with a subset of these mutations resulting in reduced p53 stability. Here, the 1.55 A crystal structure of the mouse p53 core domain with a molecule of tris(hydroxymethyl)aminomethane (Tris) bound through multiple hydrogen bonds to a region of p53 shown to be important for repair of a subset of tumor-derived p53-stability mutations is reported. Consistent with the hypothesis that Tris binding stabilizes the p53 core domain, equilibrium denaturation experiments are presented that demonstrate that Tris binding increases the thermodynamic stability of the mouse p53 core domain by 3.1 kJ mol(-1) and molecular-dynamic simulations are presented revealing an overall reduction in root-mean-square deviations of the core domain of 0.7 A when Tris is bound. It is also shown that these crystals of the p53 core domain are suitable for the multiple-solvent crystal structure approach to identify other potential binding sites for possible core-domain stabilization compounds. Analysis of the residue-specific temperature factors of the high-resolution core-domain structure, coupled with a comparison with other core-domain structures, also reveals that the L1, H1-S5 and S7-S8 core-domain loops, also shown to mediate various p53 activities, harbor inherent flexibility, suggesting that these regions might be targets for other p53-stabilizing compounds. Together, these studies provide a molecular scaffold for the structure-based design of p53-stabilization compounds for development as possible therapeutic agents.
About this StructureAbout this Structure
2IOO is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution structure of the p53 core domain: implications for binding small-molecule stabilizing compounds., Ho WC, Luo C, Zhao K, Chai X, Fitzgerald MX, Marmorstein R, Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1484-93. Epub 2006, Nov 23. PMID:17139084
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