Oxygenation reactions catalyzed by the F557V mutant of soybean lipoxygenase-1: Evidence for two orientations of substrate binding

Hershelman, Dillon; Kahler, Kirsten M.; Price, Morgan J.; Lu, Iris; Fu, Yuhan; Plumeri, Patricia; Karaisz, Fred; Bassett, Natasha F.; Findeis, Peter M.; Clapp, Charles H.

doi:10.1016/j.abb.2019.108082

Cited by 4 publications

(3 citation statements)

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“…Free fatty acids can be modeled in both orientations (carboxylate-in and carboxylate-out) [28] and it now seems likely that both orientations are possible for fatty acids and variouse xperimental situations. [51] It couldb ea rgued that the lipoxygenase activation step would require the oxidizing fatty acid hydroperoxidet oh ave an orientation reversed from that of the product when it is still on the enzyme.…”

Section: Location Of the Polar End Of Lipoxygenase Substratesmentioning

confidence: 99%

“…Indeed, the narrow line widths of the EPR spectra of LOPTC monomers bound to SBL1 (Figure ) indicate fluctuations of the head group that are almost as fast as rotational motion of a small molecule in solution. Free fatty acids can be modeled in both orientations (carboxylate‐in and carboxylate‐out) and it now seems likely that both orientations are possible for fatty acids and various experimental situations . It could be argued that the lipoxygenase activation step would require the oxidizing fatty acid hydroperoxide to have an orientation reversed from that of the product when it is still on the enzyme.…”

Section: Spin Label Studies Of Lipoxygenasementioning

confidence: 99%

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EPR Spectroscopic Studies of Lipoxygenases

Gaffney

2019

Chemistry An Asian Journal

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Polyunsaturated fatty acids are sources of diverse natural, and chemically designed products. The enzyme lipoxygenase selectively oxidizes fatty acid acyl chains using controlled free radical chemistry; the products are regio‐ and stereo‐chemically unique hydroperoxides. A conserved structural fold of ≈600 amino acids harbors a long and narrow substrate channel and a well‐shielded catalytic iron. Oxygen, a co‐substrate, is blocked from the active site until a hydrogen atom is abstracted from substrate bis‐allylic carbon, in a non‐heme iron redox cycle. EPR spectroscopy of ferric intermediates in lipoxygenase catalysis reveals changes in the metal coordination and leads to a proposal on the nature of the reactive intermediate. Remarkably, free radicals are so well controlled in lipoxygenase chemistry that spin label technology can be applied as well. The current level of understanding of steps in lipoxygenase catalysis, from the EPR perspective, will be reviewed.

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Section: Location Of the Polar End Of Lipoxygenase Substratesmentioning

confidence: 99%

Section: Spin Label Studies Of Lipoxygenasementioning

confidence: 99%

EPR Spectroscopic Studies of Lipoxygenases

Gaffney

2019

Chemistry An Asian Journal

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“…However, significant alterations to the ligand environment surrounding the metal center were observed in this structure, including a direct coordination of the hydroperoxide product to the metal center. The head-to-tail orientation of the product and its relevance to productive substrate binding in SLO-1 remains contentious [21,[30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid Allosteric Regulation of C-H Activation in Plant and Animal Lipoxygenases

Offenbacher

Holman

2020

Molecules

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Lipoxygenases (LOXs) catalyze the (per) oxidation of fatty acids that serve as important mediators for cell signaling and inflammation. These reactions are initiated by a C-H activation step that is allosterically regulated in plant and animal enzymes. LOXs from higher eukaryotes are equipped with an N-terminal PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain that has been implicated to bind to small molecule allosteric effectors, which in turn modulate substrate specificity and the rate-limiting steps of catalysis. Herein, the kinetic and structural evidence that describes the allosteric regulation of plant and animal lipoxygenase chemistry by fatty acids and their derivatives are summarized.

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