Lipoxygenases – Structure and reaction mechanism

Andreou, Alexandra Z.; Feußner, Ivo

doi:10.1016/j.phytochem.2009.05.008

Cited by 343 publications

(278 citation statements)

References 58 publications

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“…The lipoxygenase family (LOXs; EC 1.13.11.12) includes non-gemic iron-compatible dioxygenases, which catalyze regio-and stereo dioxygenation of polyunsaturated fatty acid (PUFA) with one or several cis, cis-1,4-pentadiene fragments and production of fatty acid hydroperoxides [5,6,11]. The mammal LOXs classification is based on the oxidation specificity of arachidonic acid.…”

Section: Lipoxygenase General Characteristicmentioning

confidence: 99%

Lipoxygenases and their metabolites in formation of plant stress tolerance

Бабенко¹,

Shcherbatiuk²,

Skaterna³

et al. 2017

Ukr.Biochem.J.

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Section: Lipoxygenase General Characteristicmentioning

confidence: 99%

Lipoxygenases and their metabolites in formation of plant stress tolerance

Бабенко¹,

Shcherbatiuk²,

Skaterna³

et al. 2017

Ukr.Biochem.J.

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“…The diversity is such that individual LOX enzymes are known that can account for oxygenation on almost all the available positions on the common polyunsaturated fatty acid substrates (3)(4)(5). The different members of the LOX superfamily, whether prokaryotic, plant, fungal, invertebrate, or vertebrate/mammalian, all retain the same conserved amino acids at the catalytic center and share a common structural framework (6 -12).…”

Section: Lipoxygenases (Lox)mentioning

confidence: 99%

Crystal Structure of a Lipoxygenase in Complex with Substrate

Neau

Bender

Boeglin

et al. 2014

Journal of Biological Chemistry

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Background: Lipoxygenases (LOX) catalyze the oxygenation of polyunsaturated fatty acids but generate distinct products from a common substrate. Results: We report the first structure of a LOX-substrate complex. Conclusion:The structure provides a context for understanding product specificity in enzymes that metabolize arachidonic acid. Significance: With roles in the production of potent lipid mediators, LOX are targets for drug design.

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“…2 catalyze the peroxidation of free and/or esterified polyunsaturated fatty acids to corresponding hydroperoxy compounds (1,2). They constitute a heterogeneous family of lipid metabolizing enzymes and have been implicated in the pathogenesis of inflammatory (3,4), degenerative (5,6), and hyperproliferative (7,8) diseases.…”

Section: Lipoxygenases (Loxs)mentioning

confidence: 99%

Molecular Basis for the Reduced Catalytic Activity of the Naturally Occurring T560M Mutant of Human 12/15-Lipoxygenase That Has Been Implicated in Coronary Artery Disease

Schurmann

Anton

Ivanov

et al. 2011

Journal of Biological Chemistry

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Lipoxygenases have been implicated in cardiovascular disease. A rare single-nucleotide polymorphism causing T560M exchange has recently been described, and this mutation leads to a near null variant of the enzyme encoded for by the ALOX15 gene. When we inspected the three-dimensional structure of the rabbit ortholog, we localized Thr-560 outside the active site and identified a hydrogen bridge between its side chain and Gln-294. This interaction is part of a complex hydrogen bond network that appears to be conserved in other mammalian lipoxygenases. Gln-294 and Asn-287 are key amino acids in this network, and we hypothesized that disturbance of this hydrogen bond system causes the low activity of the T560M mutant. To test this hypothesis, we first mutated Thr-560 to amino acids not capable of forming side chain hydrogen bridges (T560M and T560A) and obtained enzyme variants with strongly reduced catalytic activity. In contrast, enzymatic activity was retained after T560S exchange. Enzyme variants with strongly reduced activity were also obtained when we mutated Gln-294 (binding partner of Thr-560) and Asn-287 (binding partner of Gln-294 and Met-418) to Leu. Basic kinetic characterization of the T560M mutant indicated that the enzyme lacks a kinetic lag phase but is rapidly inactivated. These data suggest that the low catalytic efficiency of the naturally occurring T560M mutant is caused by alterations of a hydrogen bond network interconnecting this residue with active site constituents. Disturbance of this bonding network increases the susceptibility of the enzyme for suicidal inactivation.

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Lipoxygenases – Structure and reaction mechanism

Cited by 343 publications

References 58 publications

Lipoxygenases and their metabolites in formation of plant stress tolerance

Lipoxygenases and their metabolites in formation of plant stress tolerance

Crystal Structure of a Lipoxygenase in Complex with Substrate

Molecular Basis for the Reduced Catalytic Activity of the Naturally Occurring T560M Mutant of Human 12/15-Lipoxygenase That Has Been Implicated in Coronary Artery Disease

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