2ioi: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2ioi.gif|left|200px]] | [[Image:2ioi.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_2ioi", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
--> | |||
{{STRUCTURE_2ioi| PDB=2ioi | SCENE= }} | |||
}} | |||
'''Crystal structure of the mouse p53 core domain at 1.55 A''' | '''Crystal structure of the mouse p53 core domain at 1.55 A''' | ||
| Line 31: | Line 28: | ||
[[Category: Marmorstein, R.]] | [[Category: Marmorstein, R.]] | ||
[[Category: Zhao, K.]] | [[Category: Zhao, K.]] | ||
[[Category: | [[Category: Ig fold]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:43:23 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 07:43, 4 May 2008
Crystal structure of the mouse p53 core domain at 1.55 A
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
2IOI 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 Page seeded by OCA on Sun May 4 07:43:23 2008