Human lipoxygenases (LOXs) are the enzymes participating in the metabolism of the polyunsaturated fatty acids and catalyzing
their oxidation to a variety of eicosanoids, which as the secondary signal transducers have a major impact on human homeostasis.
They are involved in many diseases such as inflammatory responses, cancers, cardiovascular and kidney diseases, neurodegenerative disorders
and metabolic syndrome. This review summarizes recent developments concerning human 12S-LOX and rabbit 15-LOX projected
upon available structural data of LOX and COX oxidoreductases, with conclusions that might apply to LOX family of enzymes in general.
Namely: (i) Human lipoxygenases might act as oligomers consisting of active and apo monomers. (ii) Sequential homodimers might
act as structural heterodimers with the dimeric interface formed by the interactions resembling the leucine zipper in the coiled-coil superstructure.
(iii) Two commonly recognized domains are not sufficient to explain LOX flexibility. Molecular architecture should contain
assignment of another regulatory domain of alpha-beta character, possibly important in molecular signaling, which might provide another
avenue for targeted drug development. (iv) Allosteric mechanism might involve orchestrated conformational changes and flexibility of
the coils connecting the structured elements and ligands binding in more than one monomer.
Keywords: Allosteric mechanism, fatty acid metabolism, lipoxygenase, protein domain architecture, structural heterodimers, LOX, COX, oxidoreductases, polyunsaturated fatty acids, eicosanoids
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