Probing conformational changes in lipoxygenases upon membrane binding: Fine-tuning by the active site inhibitor ETYA

Almerinda Di Venere, Eleonora Nicolai, Igor Ivanov, Enrico Dainese, Susan Adel, B. C. Angelucci, Hartmut Kuhn, Mauro Maccarrone, Giampiero Mei

Research output: Contribution to journalArticlepeer-review


Lipoxygenases (LOXs) are lipid-peroxidizing enzymes that are involved in the metabolism of polyunsaturated fatty acids. Their biological activity includes a membrane binding process whose molecular details are not completely understood. The mechanism of enzyme-membrane interactions is thought to involve conformational changes at the level of the protein tertiary structure, and the extent of such alterations depends on the degree of structural flexibility of the different LOX isoforms. In this study, we have tested the resilience properties of a plant and a mammalian LOX, by using high pressure fluorescence measurements at different temperatures. The binding of LOXs to the lipid bilayer has been characterized using both large and giant unilamellar vesicles and electron transfer particles (inner mitochondrial membranes) as model membranes. The data indicate that the degree of LOXs' flexibility is strictly dependent on the two distinct N- and C-terminal domains that characterize the 3D structure of these enzymes. Furthermore, they demonstrate that increasing the rigidity of protein scaffolding by the presence of an active site ligand impairs the membrane binding ability of LOXs. These findings provide evidence that the amphitropic nature of LOXs is finely tuned by the interaction of the substrate with the residues of the active site, suggesting new strategies for the design of enzyme inhibitors.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number1
Publication statusPublished - 2014


  • Fluorescence dynamics
  • High pressure
  • Lipoxygenases
  • Motional flexibility

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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