Journal
CURRENT MEDICINAL CHEMISTRY
Volume 19, Issue 30, Pages 5122-5127Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986712803530520
Keywords
Allosteric mechanism; fatty acid metabolism; lipoxygenase; protein domain architecture; structural heterodimers
Funding
- Frederick M. Douglass Foundation
- King Saud University Protein Research Chair program
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available