Figure (A) The substrate adopts a horseshoe shape in the U-shaped channel (stereo). The side chains of highly conserved amino acids line the base of the active site, along with Gly-427. Glu-430, part of an inter-helical charge cluster that includes the substrate carboxylate, is shown in line rendering. The Fe2+ (transparent rust sphere) is positioned behind the substrate. (B) Detail of the superposition of inhibitors (rotated ∼180° with respect to (A)) observed in 15-LOX-2 (red) 12-LOX (gold C, red O) and 15-LOX-1 (teal C, red O). The 15-LOX-2 and 12-LOX inhibitors conform to the arachidonic acid placement, while the 15-LOX-1 inhibitor overlaps partially. The Fe2+, solid rust sphere, is in front of the substrate in this view. An interactive view is available in the electronic version of the article.