Cdk2 is one of the smallest kinases known. Monomeric, unphosphorylated Cdk2 is an inactive 33kd catalytic subunit of a larger holoenzyme. For activation to occur, Cdk2 must be bound to cyclin, its regulatory subunit, and be phosphorylated by the Cdk-activating kinase (CAK) at a conserved threonine residue (T160), located in the T loop. Cdk2 has been crystalized as an apoenzyme,in a complex with Mg2+ATP, and while bound to the cell cycle-regulatory protein CksHs1.
Cdk2 is comprised of two lobes. The smaller N-terminal lobe contains one alpha-helix and a highly conserved five stranded beta-sheet. The substrate binds to the larger lobe, which has six alpha-helices and one small beta sheet. T160 is located on the larger lobe. The core of Cdk2 looks similar to the catalytic subunit of cAMP-dependent protein kinase (cAPK).
ATP binds to residues that are exposed in the cleft between the two lobes. The adenine is placed between the beta-sheet of the small lobe and the L7 loop between beta-strands 5 and 2. Lys33, Asp145, and amides in the backbone of the glycine-rich loop hold the phosphates in place. The Mg2+ion has an octahedral co-ordination that is enforced by an oxygen from each of the three phosphates, and by Asp145, Asn132, and a water molecule. When ATP binds Cdk2, the cleft closes slightly.