The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity

Nat Struct Biol. 1997 Dec;4(12):1003-9. doi: 10.1038/nsb1297-1003.

Abstract

Here we report the first structure of a mammalian 15-lipoxygenase. The protein is composed of two domains; a catalytic domain and a previously unrecognized beta-barrel domain. The N-terminal beta-barrel domain has topological and sequence identify to a domain in the mammalian lipases, suggesting that these domains may have similar functions in vivo. Within the C-terminal domain, the lipoxygenase substrate binding site is a hydrophobic pocket defined by a bound inhibitor. Arachidonic acid can be docked into this deep hydrophobic pocket with the methyl end extending down into the bottom of the pocket and the acid end tethered by a conserved basic residue on the surface of the enzyme. This structure provides a unifying hypothesis for the positional specificity of mammalian lipoxygenases.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonate 15-Lipoxygenase / chemistry*
  • Arachidonate 15-Lipoxygenase / metabolism
  • Arachidonate 5-Lipoxygenase / chemistry
  • Arachidonate 5-Lipoxygenase / metabolism
  • Arachidonic Acid
  • Binding Sites
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Fatty Acid-Binding Proteins
  • Lipase / chemistry*
  • Lipase / genetics
  • Models, Molecular
  • Myelin P2 Protein / chemistry
  • Myelin P2 Protein / metabolism
  • Neoplasm Proteins*
  • Protein Structure, Secondary
  • Rabbits
  • Substrate Specificity

Substances

  • Carrier Proteins
  • Fatty Acid-Binding Proteins
  • Myelin P2 Protein
  • Neoplasm Proteins
  • Arachidonic Acid
  • Arachidonate 15-Lipoxygenase
  • Arachidonate 5-Lipoxygenase
  • Lipase