Figure 3

Binding of p27 with cyclin A and CDK2. (a,b) Interaction of p27 (yellow) with cyclin A (purple). (a) Electrostatic surface potential of cyclin A revealing binding of the p27 N-terminus in a shallow groove along the cyclin box repeat. The conserved p27 Leu-Phe-Gly sequence binds in a deeper, more hydrophobic groove. (b) Ribbon and density (at 6.0σ, threshold 0.205) diagram of p27 binding to the ⍺-helices of the cyclin box repeat of cyclin A, where residues Ala28, Arg30 and Asn31 of p27 form hydrogen bonds with Trp127, Glu220 and Gln254 of cyclin A respectively. (c,d) Binding of p27 (yellow) with CDK2 (blue). (c) Electrostatic surface potential of CDK2 showing how p27 (density at 6.0σ, threshold 0.221) extends over CDK2 into the catalytic cleft, with residues Trp60, Phe64, Phe62, Tyr74 and Trp76 of p27 interacting with CDK2 (d) p27 3₁₀ helix (residues 85–93) binds through the catalytic cleft of CDK2 and into the ATP binding site where p27 Tyr88 hydrogen bonds with the backbone of CDK2 Glu81 (density map at 8.8σ, threshold 0.315).