Fig. 26.4 Based on the crystal structure of a cAMP-dependent kinase with a bound ADP and aluminum trifluoride as a transition-state mimetic, the reaction steps of the phosphate group transfer from ATP (red) to the serine residue of the substrate (blue) can be modeled. Asp184 from the DFG loop is coordinated to the β- and γ-phosphate groups of ATP via a magnesium ion. An additional Mg2+ helps to position the three phosphate groups correctly. Serine 21, which is to be phosphorylated, nucleophilically attacks the terminal γ-phosphate group, and a phosphorus atom is transferred with formation of a trigonal bipyramidal intermediate. The neighboring Asp166 takes the proton from Ser21 OH during this reaction step. At the same time, the positively charged residues Lys168 of the kinase and Arg18 of the substrate stabilize this intermediate.