PDBsum entry 2ioi

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Transcription, antitumor protein PDB id
Protein chain
187 a.a. *
Waters ×249
* Residue conservation analysis
PDB id:
Name: Transcription, antitumor protein
Title: Crystal structure of the mouse p53 core domain at 1.55 a
Structure: Cellular tumor antigen p53. Chain: a. Fragment: core domain, residues 92-292. Synonym: tumor suppressor p53. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: tp53, p53, trp53. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
1.55Å     R-factor:   0.184     R-free:   0.228
Authors: W.C.Ho,C.Luo,K.Zhao,X.Chai,M.X.Fitzgerald,R.Marmorstein
Key ref:
W.C.Ho et al. (2006). High-resolution structure of the p53 core domain: implications for binding small-molecule stabilizing compounds. Acta Crystallogr D Biol Crystallogr, 62, 1484-1493. PubMed id: 17139084 DOI: 10.1107/S090744490603890X
10-Oct-06     Release date:   05-Dec-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q8C526  (Q8C526_MOUSE) -  Cellular tumor antigen p53 (Fragment)
314 a.a.
187 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     apoptotic process   2 terms 
  Biochemical function     transcription regulatory region DNA binding     3 terms  


DOI no: 10.1107/S090744490603890X Acta Crystallogr D Biol Crystallogr 62:1484-1493 (2006)
PubMed id: 17139084  
High-resolution structure of the p53 core domain: implications for binding small-molecule stabilizing compounds.
W.C.Ho, C.Luo, K.Zhao, X.Chai, M.X.Fitzgerald, R.Marmorstein.
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.
  Selected figure(s)  
Figure 1.
Figure 1 Overall structure of the mouse p53 core domain. (a) Representative F[o] - F[c] OMIT electron-density map of residues 231-233 contoured at 3.5 . (b) Overall structure of the mouse p53 core domain solved to 1.55 Å resolution. The Zn atom is shown as a yellow sphere and a molecule of Tris is shown in red. (c) Overlay of the mouse core domain solved at 1.55 Å resolution in space group C2 (HR, green), the mouse p53 core domain solved at 2.7 Å in space group C222[1] (PDB code 1hu8 , grey) and the human p53 core domain unbound to DNA (PDB code 1tsr ; orange).
Figure 3.
Figure 3 Location of a 2-propanol molecule bound to the mouse p53 core domain. (a) Density surrounding the location of the 2-propanol-binding site. Blue density, F[o, 2-propanol] - F[o, native] at the 2.5 level. (b) F[o] - F[c] OMIT map calculated at 2.5 using the final structure with 2-propanol omitted. Red density, F[o, native] - F[o, 2-propanol]; blue spheres, water molecules observed in native structure; green sphere, water observed in 2-propanol-soaked structure; orange dashes, hydrogen bonding. (c) Surface representation of the 2-propanol-binding site with 2-propanol shown as a stick figure. The 2-propanol-binding site is denoted by an arrow. C, O and N atoms are colored green, red and blue, respectively.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 1484-1493) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19748724 Y.H.Tan, Y.M.Chen, X.Ye, Q.Lu, V.Tretyachenko-Ladokhina, W.Yang, D.F.Senear, and R.Luo (2009).
Molecular mechanisms of functional rescue mediated by P53 tumor suppressor mutations.
  Biophys Chem, 145, 37-44.  
18410249 A.C.Joerger, and A.R.Fersht (2008).
Structural biology of the tumor suppressor p53.
  Annu Rev Biochem, 77, 557-582.  
18366598 C.J.Oldfield, J.Meng, J.Y.Yang, M.Q.Yang, V.N.Uversky, and A.K.Dunker (2008).
Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners.
  BMC Genomics, 9, S1.  
17876829 E.Kwon, D.Y.Kim, S.W.Suh, and K.K.Kim (2008).
Crystal structure of the mouse p53 core domain in zinc-free state.
  Proteins, 70, 280-283.
PDB code: 2p52
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