Fig. 3.
Proposed model for the correlation between phosphorylation of the activation loop and the active configuration of the DFG motif. (A) DFG -glycine moves out its amide nitrogen upon inactivation breaking a conserved hydrogen bond to the DFG aspartate (dashed red line). Cdk2 structures were used for the illustration (magenta, active; cyan, inactive; see Table 1). (B) Alignment (main chain atoms only) of the magnesium-binding loops of 23 active kinases (Table 2) demonstrates conserved geometry for this part of the activation segment. Two conserved hydrogen bonds are shown as red arrows. One is between DFG aspartate and the DFG glycine; the other is a 3-turn between the DFG phenylalanine and the DFG + 2 residue. (C) A cascade of conserved hydrogen bonds connecting the phosphorylation site of PKA and the catalytically important DFG aspartic acid (I–IV). Carbons of the activation loop are colored white; carbons of the catalytic loop are colored tan; carbons of the β7–β8 sheet, which precedes the DFG motif, are colored green. The six Cα atoms of the magnesium-binding loop are shown as spheres, the immobilized atoms are colored tan, and the rest are colored yellow. Two peptide bonds, which are able to rotate around Cα atoms, are shown as blue planes.