An ensemble of lipoxygenase structures reveals novel conformations of the Fe coordination sphere

Protein Sci. 2019 May;28(5):920-927. doi: 10.1002/pro.3602. Epub 2019 Apr 3.

Abstract

The regio- and stereo-specific oxygenation of polyunsaturated fatty acids is catalyzed by lipoxygenases (LOX); both Fe and Mn forms of the enzyme have been described. Structural elements of the Fe and Mn coordination spheres and the helical catalytic domain in which the metal center resides are highly conserved. However, animal, plant, and microbial LOX each have distinct features. We report five crystal structures of a LOX from the fungal plant pathogen Fusarium graminearum. This LOX displays a novel amino terminal extension that provides a wrapping domain for dimerization. Moreover, this extension appears to interfere with the iron coordination sphere, as the typical LOX configuration is not observed at the catalytic metal when the enzyme is dimeric. Instead novel tetra-, penta-, and hexa-coordinate Fe2+ ligations are apparent. In contrast, a monomeric structure indicates that with repositioning of the amino terminal segment, the enzyme can assume a productive conformation with the canonical Fe2+ coordination sphere.

Keywords: enzymes; lipid oxidation; lipoxygenase; protein structure; x-ray crystallography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism
  • Fusarium / chemistry
  • Fusarium / enzymology*
  • Iron / metabolism*
  • Lipoxygenases / chemistry*
  • Lipoxygenases / metabolism*
  • Manganese / metabolism*
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Substrate Specificity

Substances

  • Fungal Proteins
  • Manganese
  • Iron
  • Lipoxygenases