National Center for
3FG3: Crystal structure of Delta413-417:GS I805W LOX
The 1.85 A structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity
Biochemistry (2009) 48 p.7906-7915» All references (2)
Lipoxygenases (LOX) play pivotal roles in the biosynthesis of leukotrienes and other biologically active eicosanoids derived from arachidonic acid. A mechanistic understanding of substrate recognition, when lipoxygenases that recognize the same substrate generate different products, can be used to help guide the design of enzyme-specific inhibitors. We report here the 1.85 A resolution structure of an 8R-lipoxygenase from Plexaura homomalla, an enzyme with a sequence approximately 40% identical to that of human 5-LOX. The structure reveals a U-shaped channel, defined by invariant amino acids, that would allow substrate access to the catalytic iron. We demonstrate that mutations within the channel significantly impact enzyme activity and propose a novel model for substrate binding potentially applicable to other members of this enzyme family.