Figure 5. Structure of the Ins(1,4,5)P₃R₁-binding site based on the X-ray crystal structure of the mouse Ins(1,4,5)P₃R₁ core binding domain.

The crystallographically observed position of bound Ins(1,4,5)P₃ [39] is shown in orange. Molecular docking experiments suggest that Ins(1,4,6)P₃ (green) may be a relatively effective mimic of Ins(1,4,5)P₃ at the Ins(1,4,5)P₃R₁-binding site because it can bind in an orientation that allows its phosphate groups to mimic the three phosphate groups of Ins(1,4,5)P₃, while its axial 2-hydroxy group is accepted by an open region close to Gly²⁶⁸. However, Ins(1,3,6)P₃ (purple) may be prevented from adopting a similar binding mode due to unfavourable steric interactions of its axial 2-hydroxy group with Arg⁵⁶⁸ and Lys⁵⁶⁹. Molecular-docking experiments were carried out using the X-ray crystal structure of the Ins(1,4,5)P₃-binding core of mouse type 1 InsP₃R in complex with Ins(1,4,5)P₃ (PDB code 1N4K [39]) according to methods previously described [43]. For clarity, six molecules of water included in the docking experiments, and the hydrogen atoms of Ins(1,4,5)P₃, Ins(1,4,6)P₃ and Ins(1,3,6)P₃ are not shown.