Figure 4.

The predicted cholesterol binding site of bNPC2. (A) Stereo view of cavities within the loosely packed hydrophobic interior of bNPC2. A surface pocket and two small internal cavities (labeled) are thought to comprise an incipient cholesterol-binding site. Side chains of residues that line these cavities (described in the text) are shown in stick representation. The side chains of Phe-66, Val-96, and Tyr-100 that have been found to be essential for cholesterol binding (9) are shown in red. (B) The proposed binding site for cholesterol. A semitransparent space-filling model of cholesterol (green) has been manually docked in the proposed sterol-binding site. Note that, despite the complementarity of cholesterol to the length and shape of the cavity, the ligand cannot fit because of steric clashes with side chains that line the pocket. Presumably, the cavity must dilate to accommodate cholesterol. Side chains and coloring scheme are as indicated in A.