Figure 3
Structural features of the active CDK12 subunit (a) Ribbon representation highlighting selected structural features of the CDK12715–1052 subunit bound to AMP-PNP (PDB ID 4CXA, chain A). (b) CDK12 adopts an active conformation as shown by the correct alignment of the hydrophobic spine (indicated residues shown as spheres). (c) Phosphorylation at CDK12 Thr893 helps to stabilize the active kinase conformation. Shown are the hydrogen bond interactions of pThr893 with Arg882 (activation loop) and Arg858 (catalytic loop) as well as the nearby interaction of Arg773 (PITAIRE motif, αC helix) with CycK Glu108. (d) Ovarian cancer-associated mutations28 that impair CDK12 activity are mapped onto the structure and are predicted to destabilize the protein fold. Sites of mutation are indicated as spheres. CycK is omitted for clarity.
