Fig. 7: In silico model templated on 7SSB for CNB-B and 7T4V for the switch helix (SW) to form the apo state of CNB-B with the switch helix packed against the domain.

a SMA1 (cyan) and cGMP (magenta) are rendered for reference in the Nest and cyclic nucleotide binding sites respectively. Surface is rendered in wire. b The switch helix is rendered in gray tube and line to facilitate visualization. Key residues of the switch helix labeled and underlined. Note the tight fit of Tyr336 within the same hydrophobic cleft as the dichlorophenyl group of SMA1. H-arene interactions occur with both Phe222 and Phe321. The helix appears to be held in place with strong salt-bridges with interactions occurring between Glu340, and Gln296 as well as maintaining the helix through a salt bridge between Lys342 and T221. An additional backbone interaction with W289 is also observed in both sets of interactions. c, d Alternate views of packed helix against CNB-B, note how the cGMP binding site is not restricted. e In the cGMP/ATP bound structure of 7T4T, with CNB-B in cyan and SW in gold, interactions with the partially disordered switch reveals that that Leu328, Ser332, and Tyr336 act to strongly chelate Trp289 which seems to be the focus of the helix interactions with the nest in the cGMP activated structure.