Structural modeling shown here predicts that G199R will alter the ionic environment at the p53 dimer-dimer interface. The X-ray coordinates for wild-type p53 were obtained from the RCSB PDB Protein Data Bank (ID 3KMD, deposited by Chen et al. (2010) ). The structures were produced using the UCSF Chimera package. A) The ribbon representation shows the quaternary structure of the p53 tetramer with bound DNA. The four p53 monomers are colored in gold (a), light blue (b), purple (c) and green (d). The DNA helix is in the center of the tetramer. P53 monomers form inter-protein contacts across the DNA axis (dimers of monomer pairs d-c and a-b), and along the DNA axis (between monomers d and a, between monomers c and b). The later are known as the "dimer-dimer" contacts. One of these interfaces is represented by a sphere between monomers d and a. G199R is located at the center of this sphere. B) This panel shows an in silico energy minimization performed within a 10Å sphere surrounding G199R. Molecular Operating Environment (MOE) was used for this analysis (release 2005.08, Chemical Computing Group, Montreal, Quebec). Energy-minimized monomers d and a are shown in magenta and cyan, respectively. The modeling predicts that the substitution of arginine for glycine at position 199 will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues (E171 and E198, respectively).
Sung et al. Diagnostic Pathology 2011 6:81 doi:10.1186/1746-1596-6-81