{"entity": "publication", "iuid": "2fdedc5402bb4246846cf6da7baf1e53", "timestamp": "2026-08-10T23:26:12.467Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2fdedc5402bb4246846cf6da7baf1e53.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2fdedc5402bb4246846cf6da7baf1e53"}}, "title": "Catalytic convergence of manganese and iron lipoxygenases by replacement of a single amino acid.", "authors": [{"family": "Wennman", "given": "Anneli", "initials": "A"}, {"family": "Jerner\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Hamberg", "given": "Mats", "initials": "M"}, {"family": "Oliw", "given": "Ernst H", "initials": "EH"}], "type": "journal article", "published": "2012-09-14", "journal": {"volume": "287", "issn": "1083-351X", "issue": "38", "pages": "31757-31765", "title": "J. Biol. Chem.", "issn-l": "0021-9258"}, "abstract": "Lipoxygenases (LOXs) contain a hydrophobic substrate channel with the conserved Gly/Ala determinant of regio- and stereospecificity and a conserved Leu residue near the catalytic non-heme iron. Our goal was to study the importance of this region (Gly(332), Leu(336), and Phe(337)) of a lipoxygenase with catalytic manganese (13R-MnLOX). Recombinant 13R-MnLOX oxidizes 18:2n-6 and 18:3n-3 to 13R-, 11(S or R)-, and 9S-hydroperoxy metabolites (\u223c80-85, 15-20, and 2-3%, respectively) by suprafacial hydrogen abstraction and oxygenation. Replacement of Phe(337) with Ile changed the stereochemistry of the 13-hydroperoxy metabolites of 18:2n-6 and 18:3n-3 (from \u223c100% R to 69-74% S) with little effect on regiospecificity. The abstraction of the pro-S hydrogen of 18:2n-6 was retained, suggesting antarafacial hydrogen abstraction and oxygenation. Replacement of Leu(336) with smaller hydrophobic residues (Val, Ala, and Gly) shifted the oxygenation from C-13 toward C-9 with formation of 9S- and 9R-hydroperoxy metabolites of 18:2n-6 and 18:3n-3. Replacement of Gly(332) and Leu(336) with larger hydrophobic residues (G332A and L336F) selectively augmented dehydration of 13R-hydroperoxyoctadeca-9Z,11E,15Z-trienoic acid and increased the oxidation at C-13 of 18:1n-6. We conclude that hydrophobic replacements of Leu(336) can modify the hydroperoxide configurations at C-9 with little effect on the R configuration at C-13 of the 18:2n-6 and 18:3n-3 metabolites. Replacement of Phe(337) with Ile changed the stereospecific oxidation of 18:2n-6 and 18:3n-3 with formation of 13S-hydroperoxides by hydrogen abstraction and oxygenation in analogy with soybean LOX-1.", "doi": "10.1074/jbc.M112.364331", "pmid": "22822060", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "M112.364331"}, {"db": "pmc", "key": "PMC3442510"}], "notes": [], "created": "2017-05-04T14:57:36.883Z", "modified": "2020-01-21T13:56:10.330Z"}