Cyclic AMP-dependent protein kinase (cAPK) catalyzes the transfer of the ? phosphoryl group of ATP to the serine hydroxyl group of a peptide chain. The use of metal-fluoride ground-state (BeF3�) and transition state (MgF3�, AlF4�, and putatively AlF30) analogues has added insight to the cAPK active site. Density functional theory calculations have been utilized to study the mechanism of phosphoryl transfer in cAPK as well as the structure and 19F NMR spectra of these ground-state and transition-state analogues. Transfer of native PO3� is associative in nature and utilizes a five-coordinate trigonal bipyramidal phosphorane transition state (TS). The relationship of the bonding in the TS to the 3-center 4-electron bonding model of stable phosphoranes will be discussed. Simulated 19F NMR chemical shifts closely match experiment and demonstrate that cAPK prioritizes constant charge (MgF3� or AlF4� analogues) over geometry (AlF3).

Computational studies of adenosine monophosphate dependent protein kinase: Phosphoryl transfer and ground- and transition-state analogs

247th National Meeting (2014)

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