Cdk2 as an apoenzyme is inactive. Cyclin A, a regulator of Cdk2, is one requirement for Cdk2 to be active. CyclinA has a conserved region, called the cyclin A box, which contains five residues which are invariant among cyclin family members. These residues include Lys266, Glu295, Leu255, Asp240, and Arg211. The cyclin A box recognizes a region in the catalytic cleft in Cdk2, and binds to it. Ile49 makes contact with cyclin. Arg50 and Arg150 on Cdk2 form hydrogen bonds with the carbonyl oxygens on the backbone of the cyclin A. This exposes Arg50 so that it can make contact with an ATP phosphate. Then the catalytic cleft of Cdk2 opens by 21 Angstroms, while the structure of cyclin A changes only slightly. The alpha-1 helix in subdomain III, containing the PSTAIRE sequence, is reoriented so that Glu51 turns away from the solvent and binds to Lys33 of the beta sheet in the N-terminal lobe. In this conformation, the interaction required for activation between Lys33, Glu51, and Arg145 can take place. Another important conformational change that takes place in Cdk2 as a result of cyclin A binding is the melting of the alpha-L12 helix. This helix, in subdomain VII, is replaced by the beta-9 strand. Thr160 in the T-loop is then exposed and ready for the CAK substrate to bind.