Fig. 5: Crystallographic overlay of the catalytic domain (CAT) with the CNB-B/SW/CAT crystal and the impact of SW on the CNB-B nest.

a Catalytic domain of PDB: 7T4V in blue ribbons is overlaid with the apo structure in gray (PDB: 6BDL) and ATP-bound in black (PDB: 6BG2) both as tubes. The kinase regions have been annotated to provide orientation and context. The observed all-atom RMSD for the domain is extremely low with much of the deviation occurring in the regulatory switch helix which exhibits a change in its exit angle of about 10°. AMP-PNP of 6BG2 is visualized in the ATP pocket. SMA3 is displayed in the nest region of CNB-B. The catalytic domain itself behaves largely as a rigid body as can be observed by the traces and by the pairwise RMSD matrix (c) of residues 360–671. When examining the SMA3 position within the nest domain (b) of CNB-B, the SW helix residues (underlined) contribute to the binding site previously observed by adding an additional surface for interactions. A339 from the helix works with L225 and T221 to complete a hydrophobic pocket occupying the phenyl substituent while the methylbenzoic acid moiety interacts with A343 and K344. The mesh surface is colored from lipophilic (green) to hydrophilic (purple).