Figure 7.

Structural concept explaining the different reaction specificities of human and mouse ALOX15B orthologs. In human ALOX15B, Asp602+Val603 (Jisaka positions) are localized at the bottom of the substrate-binding pocket, and the substrate fatty acids may penetrate the substrate-binding pocket with its methyl end ahead. Under these conditions, the bisallylic methylene C13 is localized in close proximity to the non-heme iron, and oxygen is introduced at C15 of arachidonic acid (15S-lipoxygenation). In mouse Alox15B, a Tyr+His motif is localized at the Jisaka positions. The positive charge of His604 may force inverse head-to-tail substrate alignment at the active site. Now, the bisallylic C10 of arachidonic acid is localized close to the non-heme iron, and oxygen is inserted at C8 (8S-lipoxygenation).