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Figure 10 | BMC Biochemistry

Figure 10

From: The role of the C8 proton of ATP in the catalysis of shikimate kinase and adenylate kinase

Figure 10

Phosphoryl transfer mechanism found in the adenylate kinase. Phosphoryl transfer mechanism found in adenylate kinase. The initiation of phosphoryl transfer occurs via the coordination of the AMP C6-NH2 to a carbonyl arising from the protein backbone by the “push” mechanism resulting in the protonation of C8 via the coordination of the conserved Arg128. This renders the C8-H more acidic, allowing for the protonation of the α-PO4, via the conserved Thr23 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-PO 4, changing the Mg2+ from being β-PO4 to γ-PO4 coordinated to being α-PO4 to β-PO4 coordinated. There is a concomitant binding of AMP in the second nucleotide binding site which is activated by the protonation of the N7 via the conserved Thr39 forming a carbene on the imidazole moiety causing a change in C8 hybridization from sp2 to sp3 hybridized. The carbene being stabilized by the lone pair on the coordinated Arg97. The nucleophilic attack from the oxygen on the α-PO4 of AMP creates the pentavalent intermediate and allows phosphoryl transfer. 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.

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