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Lipoxygenases (LOX) are non-heme iron dioxygenases known for metabolising unsaturated fatty acids. Their metabolites play vital role in inflammatory diseases and cancer. Many natural polyphenols show inhibitory properties toward LOXs, are very beneficial for human health, and so they are considered useful in disease prevention and treatment. In our X-ray analysis of LOX complexes with natural flavonoids we have stumbled upon less known and far less understood co-oxidative activity of this enzyme. This presentation discusses three examples, where structural analysis at ~2Å resolution revealed different inhibitor that was introduced to form the complex. All structures were refined to R<20% and deposited in the Protein Data Bank (PDB codes: 1HU9, 1JNQ, 1N8Q). Our studies concern soybean lipoxygenase-3 (isozyme #3) in complexes with (1) curcumin, (2) epigallocatechin gallate (EGCG) and (3) quercetin. Curcumin in presence of LOX undergoes X-ray induced photodegradation and turns into a ‘purple’, metastabile Enz-Fe⁺³-O-O-R, showing a degradation product 4-hydroperoxy-2methoxyphenol. EGCG ester undergoes hydrolysis, loses its galloyl moiety and turns into EGC. Quercetin in LOX complex appears as its product of oxidative degradation – protocatechuic acid, without demonstrating the ‘purple’ phase. Our findings present interesting examples for unexpected meanders of a targeted drug design. They also provide illustration of co-oxidative activity of this enzyme and its very peculiar kinetic behavior, were results depend not only on the source of the enzyme and its isozyme, but also upon competition between peroxidative and co-oxidative reactions.