Figure 2. Mechanism for ‘fusing’ the C-spine.

Two elements of the endogenous C-spine are fused by the adenine ring of ATP (left). We predict that the phenylalanine side chain in the A70F mutant will fill in the adenine-binding pocket (centre). In VRK3, several residues (Leu¹⁸⁰, Ser²⁰¹ and Leu²⁶²) fill in the adenine-binding pocket making it unable to bind ATP. Leu¹⁸⁰ and Ser²⁰¹ are equivalent to Val⁵⁷ and Ala⁷⁰ respectively in PKA, whereas Leu²⁶² corresponds to Val¹²³ from the hinge.