Title
The 1.85 A structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity
Document Type
Article
Publication Date
8-25-2009
Abstract
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.
Publication Source (Journal or Book title)
Biochemistry
First Page
7906
Last Page
15
Recommended Citation
Neau, D. B., Gilbert, N. C., Bartlett, S. G., Boeglin, W., Brash, A. R., & Newcomer, M. E. (2009). The 1.85 A structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity. Biochemistry, 48 (33), 7906-15. https://doi.org/10.1021/bi900084m