FIG. 6.

Community map analysis explains the dynamics-based role of inactivating mutations and substrate recognition in PKA. (a) Functional roles assigned to PKA communities based on biochemical/biophysical experiments. (b) Distinct community networks obtained for the Y204A mutation when compared with WT PKA reveals the changing of communities in the C-lobe. Specifically, changes in community E and F explain the loss of synchronization of ATP and peptide at the PKA active site. (b) Community-based segregation of dynamics in the active site of PKA is distinct for an inhibitor peptide (PKI) when compared with a substrate (PKS). PKI tightly binds the kinase (as known by experiments) by engaging with its D and F communities. PKS only engages with community F with all catalytic residues including in the same community. Figure adapted from our earlier manuscripts.^3,53