Figure 3

The allosteric profile and fluctuation correlation plots for PDK1. The correlation matrix shown as an intensity plot A, with the direct agonist contacts shown as gray bars and the activation loop as a black bar. The agonist part of the correlation matrix is expanded and shown to the right of A for clarity. There is a clear peak in the correlation at the activation loop. The distance matrix is shown in B and the allosteric sites in A are those peaks that are away from direct residue contacts. A linear allosteric profile for PS48 across the protein is shown in C, with the direct ligand contacts shown as grey bars and the activation loop as a black bar above the graph. The highest correlation in the large lobe is at the activation loop. When the agonist is removed from the crystal and the correlation of the would be agonist interacting residues in the PIF pocket with the rest of the protein is calculated the peak shifts to residue THR255 away from the activation loop, D. Note, the correlation profiles have been scaled to average zero and have a standard deviation of unity.