Figure 9

Phosphoryl transfer mechanism found in the shikimate kinase. Phosphoryl transfer mechanism found in shikimate kinase. The initiation of phosphoryl transfer occurs via the coordination of the ATP C6-NH₂ to a carbonyl arising from the protein backbone by the “push” mechanism resulting in the protonation of C8 via the coordination of a conserved Arg. This renders the C8-H more acidic, allowing for the protonation of the α-PO₄, via the conserved Thr17 carrier. There is a concomitant transfer of an H⁺ from the α-PO₄ to β-PO₄ via a conserved Arg, thereby facilitating the formation of the pentavalent intermediate between the γ-PO₄ and the substrate nucleophile. There is a simultaneous ATP-mediated deprotonation of the substrate -OH, allowing for the nucleophilic attack by the substrate to create the pentavalent intermediate and allow phosphoryl transfer. A protonated Lys then transfers the proton to the γ-PO₄, changing the Mg²⁺ from being β-PO₄ to γ-PO₄ coordinated to being α-PO₄ to β-PO₄ coordinated. The H⁺ originally arising from the C8 is then transferred back to C8, allowing the electron density of the adenyl moiety to return to the “ground-state” distribution.