English: "Schematic for the regulation of AMPK by kinase domain and CBM tethering to the regulatory fragment. The right-hand panel represents the activated full-length AMPK/991 complex reported in this paper. It consists of the regulatory fragment (R) containing the γ-subunit (in pink) and the C-termini scaffold domains of the α- and β-subunits (in light blue/green). The α2 kinase domain (phosphorylated on Thr-172 of the activation loop) is shown in yellow and is connected to the regulatory fragment by a flexible linker (in black). The interaction of the kinase domain with the regulatory fragment mainly involves the activation loop and protects Thr-172 from dephosphorylation. The CBM of the β-subunit (coloured in green) binds to the N-lobe of the kinase domain and is also connected to the regulatory fragment by a flexible linker (in black). The presence of the activator compound 991 (Act) is envisaged to strengthen the interaction between the kinase and CBM and protect a major proportion of the active enzyme against dephosphorylation. Dissociation of the activator compound gives rise to the species shown in the middle panel. In this case the enzyme becomes less active because the interaction between the CBM and the kinase domain is weaker and they therefore interact for a smaller proportion of the time. Replacing ADP (or AMP) by Mg.ATP leads to displacement of the α-hook and thus the dissociation of the kinase domain and CBM from the regulatory fragment (as shown in the left panel). In this form, the kinase is no longer allosterically activated and is susceptible to dephosphorylation, and thus inactivation." Figure 4d from B.Xiao et al. "Structural basis of AMPK regulation by small molecule activators" Nature Communications 4 doi:10.1038/ncomms4017 . Image and description copied under CC-BY 3.0 licence.