PSTAIRE helix

Figure 6.18 The PSTAIRE helix undergoes a major conformational change when CDK2 binds to cyclin A. In the inactive free CDK2 (yellow) the active site residue Glu 51 is far from the active site. Upon binding of cyclin A to CDK2 the PSTAIRE helix (hiue) rotates 90° and changes its position so that Glu 51 becomes positioned into the active site. (Adapted from P.D. Jeffry et al.. Nature 376 313-320, 1995.)...

On binding to the Cdk, the a5 helix of cyclin A re-orients the PSTAIRE helix of Cdkl, opening the active site cleft. (PSTAIRE is proline, serine, threonine, alanine, isoleucine, arginine, glutamic acid). 

Fig. 7.4 Alignment of the activity modulation sites of protein kinases (after Hubbard and Till, 2000). Close-up of the critical elements of protein kinase control as found in active kinase structures, represented here by the structure of active protein kinase A. The phosphothreonine acts as an organizing center that forms contacts to Arg 165 which is neighboured to the katalytic D166 and to the C-helix. The C-helix forms a salt bridge to K72 which helps to coordinate the a- and fi- phosphates of ATP correctly. This helix corresponds to the PSTAIRE helix of CDK2 (see Chapter 13) and is the focus of several regulatory mechanisms among protein kinases. In inactive kinase structures, two or more of the critical activity modulation sites are misaligned or blocked by intra- or extramolecular interaction.

Fig. 13.8 Active and inactive Cyclin-dependent protein kinase structures. The structures shown correspond to non-activated (monomeric CDK2), partially active (CDK2-cyclinA complex), fully activated (Thrl60-phosphorylated CDK2-cyclinA complex) inhibited (p27-CDK2-cyclinA complex) and non-activatable (pl6-CDK6) complex) states. In the monomeric CDK2 and cyclinA-bound structures, the PSTAIRE helix is highlighted in red and the T loop in yellow. In the phosphorylated CDK2-cyclinA complex, the T-loop is in yellow and the phosphate group is indicated by a yellow sphere. Where present, ATP is shown in ball-and stick-representation. From Pavletich (1999), with permission.

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