Structure conservation in lipoxygenases: Structural analysis of soybean lipoxygenase-1 and modeling of human lipoxygenases

S. T. Prigge, J. C. Boyington, B. J. Gaffney, L. M. Amzel

Research output: Contribution to journalArticle


Lipoxygenases are a class of non-heme iron dioxygenases which catalyze the hydroperoxidation of fatty acids for the biosynthesis of leukotrienes and lipoxins. The structure of the 839-residue soybean lipoxygenase-1 was used as a template to model human 5-, 12-, and 15-lipoxygenases. A distance-based algorithm for placing side chains in a low homology environment (only the four iron ligands were fixed during side chain placement) was devised. Twenty-six of the 56 conserved lipoxygenase residues were grouped in four distinct regions of the enzyme. These regions were analyzed to discern whether the side chain interactions could be duplicated in the models or whether alternate conformers should be considered. The effects of site directed mutagenesis variants were rationalized using the models of the human lipoxygenases. In particular, variants which shifted positional specificity between 12-and 15-lipoxygenase activity were analyzed. Analysis of active site residues produced a model which accounts for observed lipoxygenase positional specificity and stereospecificity.

Original languageEnglish (US)
Pages (from-to)275-291
Number of pages17
JournalProteins: Structure, Function and Genetics
Issue number3
StatePublished - Apr 3 1996



  • 12-lipoxygenases
  • 15- lipoxygenases
  • 5-lipoxygenases
  • arachidonic acid metabolism
  • homology modeling
  • leukotrienes
  • lipoxins
  • side chain placement

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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