Data for ligand orientation in the second binding site were obtained as described in the Figure 5 legend. Analogs are depicted as stick models. Atoms are colored blue for nitrogen, red for oxygen and orange for phosphorus. Panel A superimposes 5-PA-InsP5 (1) (carbons colored gray) and 2-O-Bn-5-PA-InsP4 (2) (carbons in cyan). Panel B and C superimpose 2,5-di-O-Bn-InsP4 (10) (carbons colored green) and 2-O-Bn-5-PA-InsP4 (2) (carbons in cyan). Arrows in panel B emphasize spatial separation, and panel C includes details of ligand interactions with neighboring amino-acid residues. Panels D and E illustrate that transfer of 5-PA-InsP5 (1) between the two sites involves a lateral migration of 7 A, a ring flip, and a rotation of about 100. Atoms are colored blue for nitrogen, red for oxygen, orange for phosphorus, and gray for carbon. The inositol ring is numbered.