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Issue 8, 2014
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Theoretical studies of cyclic adenosine monophosphate dependent protein kinase: native enzyme and ground-state and transition-state analogues

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Abstract

The mechanisms of phosphoryl transfer enzymes have garnered considerable attention. Cyclic AMP-dependent protein kinase (cAPK) catalyzes the transfer of the γ phosphoryl group of ATP to the serine hydroxyl group of a peptide chain. Metal-containing fluoro species have been used as transition-state and ground-state analogues in a variety of phosphoryl transfer enzymes and have shed light on the nature of the requirements in the active site to catalyze phosphoryl transfer. For cAPK, we present computational studies of the mechanism of phosphoryl transfer and the structure and 19F NMR spectra of various ground- (BeF3) and transition-state (MgF3, AlF4, and AlF30) analogues. With native substrate, the phosphoryl transfer proceeds through a five-coordinate phosphorane transition state, i.e., there is not a five-coordinate phosphorane intermediate. Comparisons of simulated and experimental 19F NMR spectra show cAPK prefers a monoanionic analogue (MgF3 or AlF4) over a neutral analogue (AlF3), supporting the charge balance hypothesis.

Graphical abstract: Theoretical studies of cyclic adenosine monophosphate dependent protein kinase: native enzyme and ground-state and transition-state analogues

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Publication details

The article was received on 27 Aug 2013, accepted on 28 Oct 2013 and first published on 08 Nov 2013


Article type: Communication
DOI: 10.1039/C3DT52358F
Citation: Dalton Trans., 2014,43, 3039-3043
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    Theoretical studies of cyclic adenosine monophosphate dependent protein kinase: native enzyme and ground-state and transition-state analogues

    K. N. Leigh and C. E. Webster, Dalton Trans., 2014, 43, 3039
    DOI: 10.1039/C3DT52358F

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