| (a) Amino-acid sequences of major Cdks controlling the cell cycle in humans (H. sapiens (Hs) Cdk1 and Cdk2) and yeast (S. pombe (Sp) Cdk1 and S. cerevisiae (Sc) Cdk1). Yellow residues are identical in all four kinases. Above the alignment, secondary structure elements in human Cdk2 are shown for comparison with the tertiary structure in panel (b). Key landmarks are highlighted, including the PSTAIRE or α1 helix, the inhibitory phosphorylation sites Thr 14 and Tyr 15, the activating phosphorylation site (Thr 160 in human Cdk2) and the T-loop or activation loop where Thr 160 is found. (b) Tertiary structure of human Cdk2, determined by X-ray crystallography. Like other protein kinases, Cdk2 is composed of two lobes: a smaller amino-terminal lobe (top) that is composed primarily of beta sheet and the PSTAIRE helix, and a large carboxy-terminal lobe (bottom) that is primarily made up of alpha helices. The ATP substrate is shown as a ball-and-stick model, located deep within the active-site cleft between the two lobes. The phosphates are oriented outward, toward the mouth of the cleft, which is blocked in this structure by the T-loop (highlighted in green). (PDB 1hck) |
