Kinetics of Manganese Lipoxygenase with a Catalytic Mononuclear Redox Center

Su, Chao; Sahlin, Margareta; Oliw, Ernst H.

doi:10.1074/jbc.m001408200

Cited by 73 publications

(97 citation statements)

References 32 publications

(48 reference statements)

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“…At the end of lipoxygenation, 11-HPODE is transformed to 13-HPODE by Mn-LOX (15). Electron paramagnetic resonance analysis suggests that the catalytic metal redox cycles (Mn 21 /Mn 31 ) between the resting and active forms of the enzyme, in analogy with Fe-lipoxygenases, and that the metal coordinating residues are virtually identical (16)(17)(18)(19). To date, the oxygenation of bis-allylic carbons by Fe-lipoxygenases has only been reported for the recombinant lipoxygenase domain of allene oxide synthase of Plexaura homomalla, which transforms 20:3n-6 to the bis-allylic hydroperoxide at C-10 (?5%) and to the allylic hydroperoxide at C-8 (20).…”

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Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase

Oliw

2008

Journal of Lipid Research

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Manganese lipoxygenase (Mn-LOX) catalyzes the rearrangement of bis-allylic S-hydroperoxides to allylic Rhydroperoxides, but little is known about the reaction mechanism. 1-Linoleoyl-lysoglycerophosphatidylcholine was oxidized in analogy with 18:2n-6 at the bis-allylic carbon with rearrangement to C-13 at the end of lipoxygenation, suggesting a "tail-first" model. The rearrangement of bisallylic hydroperoxides was influenced by double bond configuration and the chain length of fatty acids. The Gly316Ala mutant changed the position of lipoxygenation toward the carboxyl group of 20:2n-6 and 20:3n-3 and prevented the bis-allylic hydroperoxide of 20:3n-3 but not 20:2n-6 to interact with the catalytic metal. The oxidized form, Mn III -LOX, likely accepts an electron from the bis-allylic hydroperoxide anion with the formation of the peroxyl radical, but rearrangement of 11-hydroperoxyoctadecatrienoic acid by Mn-LOX was not reduced in D 2 O (pD 7.5), and aqueous Fe 31 did not transfer 11S-hydroperoxy-9Z,12Z,15Z-octadecatrienoic acid to allylic hydroperoxides. Mutants in the vicinity of the catalytic metal, Asn466Leu and Ser469Ala, had little influence on bis-allylic hydroperoxide rearrangement. In conclusion, Mn-LOX transforms bis-allylic hydroperoxides to allylic by a reaction likely based on the positioning of the hydroperoxide close to Mn 31 and electron transfer to the metal, with the formation of a bis-allylic peroxyl radical, b-fragmentation, and oxygenation under steric control by the protein.-Oliw, E. H. Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase. J. Lipid Res. 2008. 49: 420-428.

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Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase

Oliw

2008

Journal of Lipid Research

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“…0.3-0.7 mol of iron/mol of LOX (47). Mn-LOX on the other hand has been reported to contain 0.94 mol of manganese/mol of enzyme, while iron was below detection limit (40). Interestingly, we observed that upon expression of CspLOX2 under poor iron conditions, manganese can be incorporated in the active site.…”

Section: Discussionmentioning

confidence: 49%

“…Previous studies have shown that the metal centers of manganese and iron enzymes have otherwise similar properties (40). This rearrangement, however, has been suggested to be related to the higher redox potential of Mn 3ϩ (Mn 2ϩ % Mn 3ϩ ϩe Ϫ , ϳ1.5 V versus Fe 2ϩ % Fe 3ϩ ϩe Ϫ , 0.77 V) (51).…”

Section: Discussionmentioning

confidence: 71%

“…Besides this product, upon incubation of CspLOX2 with 18:2(n-6) a mixture of typical LOX products 13S-and 9R-HPODE were formed. So far, the only LOXs that have been reported to produce bisallylic hydroperoxides are the Mn-LOX from the fungus G. graminis (10,40) and the LOX domain of the allene oxide synthase-LOX fusion protein from the coral Plexaura homomalla, which formed the 10-hydroperoxide out of 20:3(n-6) (41). Mn-LOX is the best studied example of a bisallylic LOX and can convert 18:2(n-6) to 11S-HPODE and 13R-HPODE in a 1:3 ratio with the latter accumulating as an end product (40).…”

Section: Discussionmentioning

confidence: 99%

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A Bisallylic Mini-lipoxygenase from Cyanobacterium Cyanothece sp. That Has an Iron as Cofactor

Andreou¹,

Göbel²,

Hámberg

et al. 2010

Journal of Biological Chemistry

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Lipoxygenases are enzymes that are found ubiquitously in higher animals and plants, but have only recently been identified in a number of bacteria. The genome of the diazotrophic unicellular cyanobacterium Cyanothece sp. harbors two genes with homology to lipoxygenases. Here we describe the isolation of one gene, formerly named csplox2. It was cloned, and the protein was expressed in Escherichia coli and purified. The purified enzyme belongs to the group of prokaryotic mini lipoxygenases, because it had a molecular mass of 65 kDa. Interestingly, it catalyzed the conversion of linoleic acid, the only endogenously found polyunsaturated fatty acid, primarily to the bisallylic hydroperoxide 11R-hydroperoxyoctadecadienoic acid. This product had previously only been described for the manganese lipoxygenase from the take all fungus, Gaeumannomyces graminis. By contrast, CspLOX2 was shown to be an iron lipoxygenase. In addition, CspLOX2 formed a mixture of typical conjugated lipoxygenase products, e.g. 9R-and 13S-hydroperoxide. The conversion of linoleic acid took place with a maximum reaction rate of 31 s ؊1 . Incubation of the enzyme with [(11S)-2 H]linoleic acid led to the formation of hydroperoxides that had lost the deuterium label, thus suggesting that CspLOX2 catalyzes antarafacial oxygenation as opposed to the mechanism of manganese lipoxygenase. CspLOX2 could also oxidize diarachidonylglycerophosphatidylcholine with similar specificity as the free fatty acid, indicating that binding of the substrate takes place with a "tail-first" orientation. We conclude that CspLOX2 is a novel iron mini-lipoxygenase that catalyzes the formation of bisallylic hydroperoxide as the major product.

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“…1A). Gg-MnLOX has been extensively studied since 1998 as the prototype MnLOX (12)(13)(14)(15). The enzyme has been characterized by site-directed mutagenesis of residues, which were chosen from sequence homology to FeLOXs with known 3D structures or from sequence differences between MnLOXs with dissimilar catalytic activities (9)(10)(11)(16)(17)(18)(19).…”

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Crystal structure of linoleate 13R-manganese lipoxygenase in complex with an adhesion protein

Chen

Wennman

Karkehabadi

et al. 2016

Journal of Lipid Research

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Kinetics of Manganese Lipoxygenase with a Catalytic Mononuclear Redox Center

Abstract: Manganese lipoxygenase was isolated from the takeall fungus, Gaeumannomyces graminis, and the oxygenation mechanism was investigated.

Cited by 73 publications

References 32 publications

Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase

Factors influencing the rearrangement of bis-allylic hydroperoxides by manganese lipoxygenase

A Bisallylic Mini-lipoxygenase from Cyanobacterium Cyanothece sp. That Has an Iron as Cofactor

Crystal structure of linoleate 13R-manganese lipoxygenase in complex with an adhesion protein

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