The 1.85 Å structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity
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 ∼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. © 2009 American Chemical Society.
Publication Source (Journal or Book title)
Neau, D., Gilbert, N., Bartlett, S., Boeglin, W., Brash, A., & Newcomer, M. (2009). The 1.85 Å structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity. Biochemistry, 48 (33), 7906-7915. https://doi.org/10.1021/bi900084m