Fig. 7: Altered ligand binding site and allosteric activation upon mutation of distant, coevolving residues in the PDE5 GAFa domain.
From: Coevolving residues distant from the ligand binding site are involved in GAF domain function
A Cartoon representation of the GAFa domain highlighting helix α4 and sheet β3 from the ligand binding site that “closes” upon cGMP binding (left panel) and N-terminal helix α2 and C-terminal helix α5 that move closer upon cGMP binding (right panel). B Graphs showing probability distribution (kernel density estimation) of distances between helix α4 and sheet β3 (x-axis) and N-terminal helix α2 and C-terminal helix α5 (y-axis) of the apo (upper panel) and holo (lower panel) GAFa domain (WT and mutants) determined from a cumulative of three independent, 1000 ns-long MD simulation trajectories. Color bars, probability densities.
