Fig. 3: Comparison of the binding of SMA1 vs. trans-switch helix binding at the CNB-B nest.
From: Structural insights into selective small molecule activation of PKG1α
Overlay of 7SSR (red) and 3SHR (blue) with SMA1 (a), or the trans-chain switch helix (b) bound in the nest region of CNB-B. SMA1 is rendered in cyan sticks for reference. The ligand residues of the switch helix are comprised of F351, F352, N354, and L355 and are underlined to distinguish them from site residues. The nest is rendered with a mesh surface based on 7SSR. Residue-binding interactions between the site and the binding entity are labeled and indicated with dashed lines. Interactions with W289 and F258 are conserved, while SMA1 engages in additional interactions deeper withing the pocket including with F222 and F321. This is in addition to an interaction with Q296. Note how the dichlorophenyl moiety is positioned where F351 would normally have bound, but with increased binding interactions owing to its angle and depth. This increased level of binding interaction is consistent with its ability to displace the switch helix in partially activated PKG1α.
