Alan Brash
Last active: 3/22/2018

The 1.85 A structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity.

Neau DB, Gilbert NC, Bartlett SG, Boeglin W, Brash AR, Newcomer ME
Biochemistry. 2009 48 (33): 7906-15

PMID: 19594169 · PMCID: PMC4715880 · DOI:10.1021/bi900084m

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.

MeSH Terms (15)

Amino Acid Sequence Animals Anthozoa Binding Sites Crystallography, X-Ray Enzyme Activation Humans Intramolecular Oxidoreductases Lipoxygenase Models, Chemical Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Stereoisomerism Substrate Specificity

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