The structural basis for specificity in lipoxygenase catalysis

Newcomer, Marcia E.; Brash, Alan R.

doi:10.1002/pro.2626

Cited by 182 publications

(218 citation statements)

References 53 publications

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“…within the tentative active sites of MnLOXs, and for comparison, the active site of 8 R -LOX ( 5,42 ). The most conspicuous differences between four MnLOXs and FoMnLOX are replacement in Fo-MnLOX with Ser 348 and Leu 530 instead of Phe and Arg in the corresponding position in the other four MnLOXs.…”

Section: +mentioning

confidence: 99%

Manganese lipoxygenase of F. oxysporum and the structural basis for biosynthesis of distinct 11-hydroperoxy stereoisomers

Wennman

Magnuson

Hámberg

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org Lipoxygenases (LOXs) belong to a common gene family ( 1, 2 ). The catalytic domain is formed by ␣ -helices, which harbor fi ve metal ligands. The 3D structure is known for over 10 enzymes from plants, animals, and bacteria with 13 S -LOX of soybean LOX-1 (sLOX-1) and 8 R -LOX of Plexaura homomalla as old and new prototypes ( 3-5 ). The latter was recently crystallized with its substrate in the active site ( 5 ). Information on the active site and reaction mechanism has also been gained by site-directed mutagenesis and by analysis of various substrates, deuterated fatty acids, and LOX inhibitors ( 1, 6 ). With few exceptions, LOXs oxidize polyunsaturated fatty acids with one or more cis , cis-1,4-pentadiene units to hydroperoxides, which in many cases are precursors of biological mediators ( 1, 6, 7 ). Mammalian LOXs initiate biosynthesis of leukotrienes and epoxy alcohols, which are involved in allergic infl ammation, asthma, formation of the skin-water barrier, and cancer development ( 6,8 ). Plant LOXs form jasmonates and related oxylipins with functions in defense against pathogens and in wound healing ( 9,10 ).The N-terminal parts of mammalian and plant LOXs usually consist of ␤ -sheets with homology to polycystin-1/ LOX/ ␣ -toxin (PLAT) domains with regulatory functions. The N-terminal domains of fungal LOXs lack this homology, but they often contain a secretion signal ( 11, 12 ). Abbreviations: Af-MnLOX, Aspergillus fumigatus manganese lipoxygenase; Cg-MnLOX, Colletotrichum gloeosporioides manganese lipoxygenase; CP, chiral phase; EPR, electron paramagnetic resonance; FeLOX, iron lipoxygenase; Fo-MnLOX, Fusarium oxysporum manganese lipoxygenase; HPODE, hydroperoxyoctadecadienoic acid; 9 S -H(P)ODE, 9 S -hydro(pero) xy-10 E ,12 Z -octadecadienoic acid; 11 S -H(P)ODE, 11 S -hydro(pero)xy-9 Z ,12 Z -octadecadienoic acid; 13 R -H(P)ODE, 13 R -hydro(pero)xy-9 Z ,11 Eoctadecadienoic acid; HPOTrE, hydroperoxyoctadecatrienoic acid; 9 S -H(P)OTrE, 9 S -hydro(pero)xy-10 E ,12 Z ,15Z-octadecatrienoic acid; 11 R -H(P)OTrE, 11 R -hydro(pero)xy-9 Z ,12 Z ,15 Z -octadecatrienoic acid; 13 R -H(P)OTrE, 13 R -hydro(pero)xy-9 Z ,11 E ,15Z-octadecatrienoic acid; ICP-AES, inductively coupled plasma atomic emission spectroscopy; LOX, lipoxygenase; MnLOX, manganese lipoxygenase; Mo-MnLOX, Magnaporthe oryzae manganese lipoxygenase; RP, reversed phase; sLOX-1, soybean lipoxygenase-1; TPP, triphenylphosphine . Abstract The biosynthesis of jasmonates in plants is

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confidence: 99%

Manganese lipoxygenase of F. oxysporum and the structural basis for biosynthesis of distinct 11-hydroperoxy stereoisomers

Wennman

Magnuson

Hámberg

et al. 2015

Journal of Lipid Research

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“…The LOX mechanism is initiated with hydrogen abstraction from a bis-allylic carbon of the 1Z,4Z-pentadiene of fatty acids. This is followed by oxygen insertion, which usually produces cis-transconjugated hydroperoxy fatty acids (1,2). Plant, mammals, and a few prokaryotes express FeLOX, whereas both MnLOX and FeLOX occur in plant pathogenic fungi (5)(6)(7)(8).…”

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confidence: 99%

“…These are four structures of soybean LOX (sLOX-1, LOX-3, VLX-B, and VLX-D) (9 -13), three human LOX (15-LOX-2, 12S-LOX, and 5-LOX) (2,13,14), coral 8R-LOX and 11R-LOX (15,16), rabbit arachidonate 15-LOX-1 (17), porcine 12S-LOX (18), 15S-LOX of Pseudomonas aeruginosa (19), and linoleate 9R-LOX of Cyanotheca sp. (20).…”

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confidence: 99%

“…(20). Plant and mammalian LOX consist of two domains, a relatively small eight-stranded ␤-barrel domain with homology to the PLAT (polycystin-1, lipoxygenase, ␣-toxin) domain and a larger catalytic domain of ␣-helices containing the substratebinding channel and the catalytic iron (2). The PLAT domain appears to be absent in fungal MnLOX (5,6,(21)(22)(23).…”

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confidence: 99%

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Crystal Structure of Manganese Lipoxygenase of the Rice Blast Fungus Magnaporthe oryzae

Wennman

Oliw

Karkehabadi³

et al. 2016

Journal of Biological Chemistry

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Lipoxygenases (LOX) are non-heme metal enzymes, which oxidize polyunsaturated fatty acids to hydroperoxides. All LOX belong to the same gene family, and they are widely distributed. LOX of animals, plants, and prokaryotes contain iron as the catalytic metal, whereas fungi express LOX with iron or with manganese. Little is known about metal selection by LOX and the adjustment of the redox potentials of their protein-bound catalytic metals. Thirteen three-dimensional structures of animal, plant, and prokaryotic FeLOX are available, but none of MnLOX. The MnLOX of the most important plant pathogen, the rice blast fungus Magnaporthe oryzae (Mo), was expressed in Pichia pastoris. Mo-MnLOX was deglycosylated, purified to homogeneity, and subjected to crystal screening and x-ray diffraction. The structure was solved by sulfur and manganese single wavelength anomalous dispersion to a resolution of 2.0 Å. The manganese coordinating sphere is similar to iron ligands of coral 8R-LOX and soybean LOX-1 but is not overlapping. The Asn-473 is positioned on a short loop (Asn-Gln-Gly-Glu-Pro) instead of an ␣-helix and forms hydrogen bonds with Gln-281. Comparison with FeLOX suggests that Phe-332 and Phe-525 might contribute to the unique suprafacial hydrogen abstraction and oxygenation mechanism of Mo-MnLOX by controlling oxygen access to the pentadiene radical. Modeling suggests that Arg-525 is positioned close to Arg-182 of 8R-LOX, and both residues likely tether the carboxylate group of the substrate. An oxygen channel could not be identified. We conclude that MoMnLOX illustrates a partly unique variation of the structural theme of FeLOX. Lipoxygenases (LOX)3 are iron-or manganese-containing dioxygenases that oxidize polyunsaturated fatty acids containing one or more 1Z,4Z-pentadiene units to hydroperoxides (1, 2). These hydroperoxides are precursors of signal molecules in animals, plants, and fungi. They may take part in inflammation, asthma, cancer development, and the chemical warfare between plants, fungi, and other microorganisms (3, 4). The LOX mechanism is initiated with hydrogen abstraction from a bis-allylic carbon of the 1Z,4Z-pentadiene of fatty acids. This is followed by oxygen insertion, which usually produces cis-transconjugated hydroperoxy fatty acids (1, 2). Plant, mammals, and a few prokaryotes express FeLOX, whereas both MnLOX and FeLOX occur in plant pathogenic fungi (5-8).All LOX belong to the same gene family, but plant FeLOX, mammalian FeLOX, and fungal FeLOX and MnLOX form separate subfamilies (5, 8). The prototype MnLOX is secreted by the take-all fungus of wheat, Gaeumannomyces graminis (7). The evolution of this enzyme, 13R-MnLOX, and five members of the MnLOX subfamily are illustrated in a phylogenetic tree together with pro-and eukaryotic LOX, including fungal FeLOX (Fig. 1A).The three-dimensional structures of 11 eukaryotic and two prokaryotic FeLOX are available. These are four structures of soybean LOX (sLOX-1, LOX-3, VLX-B, and VLX-D) (9 -13), three human LOX (15-LOX-2, 12S-LOX, and 5-LOX) (2, ...

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“…Gly-332 is located at the position known as the Gly-Ala switch (1,37). Gly or Ala at this position of many FeLOX can shift the oxygenation of 18:2n-6 between C-9 and C-13 (37).…”

Section: Discussionmentioning

confidence: 99%

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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The structural basis for specificity in lipoxygenase catalysis

Cited by 182 publications

References 53 publications

Manganese lipoxygenase of F. oxysporum and the structural basis for biosynthesis of distinct 11-hydroperoxy stereoisomers

Manganese lipoxygenase of F. oxysporum and the structural basis for biosynthesis of distinct 11-hydroperoxy stereoisomers

Crystal Structure of Manganese Lipoxygenase of the Rice Blast Fungus Magnaporthe oryzae

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

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