Figure 6:

Oxidative cysteine modifications alter critical structural interactions required for BRSK allosteric regulation. Three replicates of 100 ns GROMACS molecular dynamics simulations were performed to evaluate the effects of cysteine mutation and oxidation. Salt bridge disruption was analyzed by generating contact maps representing the percentage of the simulation time in which residues were within appropriate distance (3 Angstroms). (a) T+2 Cys is located in proximity to the activation loop threonine in the T loop. (b-e) Evaluation of pT174-R140 salt bridge formation in wild type, C176A, and oxidized C176 BRSK2. (f) Location of CPE salt bridge within BRSK2. (g-j) Evaluation of E185-R258 salt bridge formation in wild type, C183A, and oxidized C183 BRSK2.