Figure 1

A. General mechanism for the induction of phosphoryl transfer from the C8H of the adenyl moiety. This is initiated via the coordination of the ATP adenyl moiety and effective proton transfer along the phosphate tail of ATP initiated from C8-H and mediated via range of conserved coordinating amino acid chains that are specific for each kinase group and family. As the KIE is a primary effect and is therefore dependent on C8-H bond breaking the C8-H is rendered more acidic by either of two mechanisms, a "push" mechanism mediated by the interaction of a backbone carbonyl at the C6-NH₂ or a "pull" mechanism mediated by the interaction via coordination of a proton donor at N7 or hydrogen bonding of C8-H to an adjacent carbonyl or alcohol (or acceptor group). The red arrows indicate direction of proton migration during the reaction. B. The "push" mechanism is initiated with the redistribution of electron density in the adenyl ring mediated by the coordination of the backbone carbonyl to C6-NH₂ via a high energy adenosine tautomer. C. The "pull" mechanism is mediated via the formation of a carbenoid species induced via the protonation of N7.