Figure 5.

For a Figure360 author presentation of this figure, see https://doi.org/10.1016/j.bpj.2020.09.019

Hotspots of synergistic allostery detected by ACF span crucial kinase motifs. (A) Heat map of synergistic allosteric effects due to dual adenosine and PIFtide binding to PDK1 as calculated by ACF mapped onto PDK1-ATP-PS48 complex (PDB: 3HRF), with ligands in green and yellow. The extent of synergism is denoted by shades of red as per key (more negative ACF equals greater synergism). Residues spanning catalytically crucial motifs of the kinase that showed synergistic effects are shown as cyan spheres. (B) Cartoon representation of PDK1 showing the observed combinatorial bidirectional allosteric effects upon dual ligand binding at the two pockets, catalytic sites, and distal GHI-subdomain locus. See also Tables S3 and S4. To see this figure in color, go online.