Figure 4

Coupled motion of αC-helix and β-phosphate in an Ire1-like kinase CDK2. (a) ATP bound to CDK2 (orange trace; CDK2 is in the inactive conformation) is, for most of its atoms, well aligned with ADP and ATP bound to a CDK2 cyclin complex (blue and green traces, respectively; CDK2 is in the active conformation), except for the β-phosphate, which is displaced by approximately 4.8 Å. (b) Key conformational rearrangements during inactive ↔ active transition in CDK2. Movement of αC-helix and E51 (1) is coupled to the movement of β-phosphate (2). The conformational change involves formation of a salt bridge between E51 and K33, formation of an interaction between K33 and β-phosphate and rotation of the γ-phosphate for in-line attack by the OH group of the substrate (small arrow connecting dashed lines indicates change in geometry) [41]. Coordinates are from PDB ID: 1hcl (apo-CDK2), 1b39 (ATP-bound CDK2), 1qmz (ATP-bound CDK2 with cyclin) and 1gy3 (ADP-bound CDK2 with cyclin). (c) The conformation of the CDK2 kinase domain in the ATP-bound state (inactive conformation with no cyclin bound) is similar to the apo-state (inactive conformation with no cyclin bound) rather than to the ADP-bound state (active conformation with cyclin bound). A corresponding comparison of several additional kinases is shown in Additional file 1, Figure S1.