Fig. 6

Crystal structure of the MDM2-p53 complex

(A) The p53 peptide (amino acids 15 to 29) is the small helix at the top. The MDM2 fragment (amino acids 17 to 125) is the large structure at the bottom that forms a deep cleft. Selected side chains are shown. Playing structural roles are residue C77 of MDM2, which is buried in a hydrophobic region and D68, which is predicted to form three intramolecular hydrogen bonds as shown. Two hydrogen bonds to backbone nitrogens of E69 and K70 and one to the Y76 side chain stabilize the middle β sheet, the other face of which contacts p53. (B) A view rotated approximately 90 degrees clockwise from that shown in A has the p53 helix at the top and part of MDM2 at the bottom. Two MDM2 residues identified as critical for the MDM2-p53 interaction by mutagenesis directly contact p53. V75 makes van der Waals contacts with F19 of p53, while G58 makes van der Waals contacts with both residues F19 and W23 of p53.