Fig. 4: Structural determinants in the ATP binding pocket.
From: Conformational motions and ligand-binding underlying gating and regulation in IP3R channel
a Cryo-EM densities (transparent gray) are overlaid with a generated model of the ATP binding site identified in the CIA-IP3R1 structure; the model is colored by domains. The ATP molecule fits to the additional density (gray mesh) observed between the ILD and LNK domains, colored blue-green and orange respectively. b Zoomed-in view of the ATP binding pocket with the ATP densities shown in gray mesh; side chain residues within 5 Å of the ATP molecule are displayed. A zinc ion (overlaid with densities at ~15σ) is located within the C2H2-like Zn2+ finger domain adjacent to the ATP binding pocket. c Conserved 3D architecture of the ATP binding pocket in CIA-IP3R1 (blue-green) and RyR1 (gold; PBD ID: 5TAP); structures are shown as thin ribbon models and ATP molecule shown in sticks. ATP within the RyR1 binding pocket is angled 40° toward the membrane plane with respect to the bound ATP in CIA-IP3R1. d, e Zoomed-in view of cryoEM density maps for CIA-IP3R1 (d) and Ca-IP3R1 (e) overlaid with their respective molecular models; cryo-EM densities corresponding two alternative side chain conformers for W2639 are clearly resolved in Ca-IP3R1 structure. ATP molecule is fit to the mesh density in ‘d’. f Schematic plot of the ATP molecule interacting with surrounding side chains in CIA-IP3R1 structure. Arcs represent hydrophobic interactions, green dashed lines are H-bonds as calculated in LigPlot+80.
