Structural highlights
Function
MNLOX_GAEAV Lipoxygenase that metabolizes linoleic and alpha-linolenic acids to 11S- and 13R-hydroperoxy fatty acids. At the end of lipoxygenation, the intermediate product 11S-HPODE from linoleic acid is then transformed into 13R-HPODE as the final product. It also acts on alpha-linolenic acid producing 11S-HPOTrE and 13R-HPOTrE with subsequent transformation of 11S-HPOTrE to 13R-HPOTrE as final product.[1]
Publication Abstract from PubMed
The crystal structure of 13R-MnLOX of Gaeumannomyces graminis (Gg) in complex with zonadhesin of Pichia pastoris was solved by molecular replacement. Zonadhesin contains beta-strands in two subdomains. A comparison of Gg-MnLOX with the 9S-MnLOX of Magnaporthe oryzae (Mo) shows that the protein fold and the geometry of the metal ligands are conserved. The U-shaped active sites differ mainly due to hydrophobic residues of the substrate channel. The volumes and two hydrophobic side pockets near the catalytic base may sanction oxygenation at C-13 and C-9, respectively. Gly-332 of Gg-MnLOX is positioned in the substrate channel between the entrance and the metal center. Replacements with larger residues could restrict oxygen and substrate to reach the active site. C18 fatty acids are likely positioned with C-11 between Mn2+OH2 and Leu-336 for hydrogen abstraction and with one side of the 12Z double bond shielded by Phe-337 to prevent antarafacial oxygenation at C-13 and C-11. Phe-347 is positioned at the end of the substrate channel and replacement with smaller residues can position C18 fatty acids for oxygenation at C-9. Gg-MnLOX does not catalyze the sequential lipoxygenation of n-3 fatty acids in contrast to Mo-MnLOX, which illustrates the different configurations of their substrate channels.
Crystal structure of linoleate 13R-manganese lipoxygenase in complex with an adhesion protein.,Chen Y, Wennman A, Karkehabadi S, Engstrom A, Oliw EH J Lipid Res. 2016 Jun 15. pii: jlr.M069617. PMID:27313058[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cristea M, Engstrom K, Su C, Hornsten L, Oliw EH. Expression of manganese lipoxygenase in Pichia pastoris and site-directed mutagenesis of putative metal ligands. Arch Biochem Biophys. 2005 Feb 1;434(1):201-11. PMID:15629124 doi:http://dx.doi.org/10.1016/j.abb.2004.10.026
- ↑ Chen Y, Wennman A, Karkehabadi S, Engstrom A, Oliw EH. Crystal structure of linoleate 13R-manganese lipoxygenase in complex with an adhesion protein. J Lipid Res. 2016 Jun 15. pii: jlr.M069617. PMID:27313058 doi:http://dx.doi.org/10.1194/jlr.M069617
