title: The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity.
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.
authors.affiliation: Graduate Group in Biophysics, University of California, San Francisco 94143-0448, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Gillmor
authors.forename: A
authors.initials: A
authors.lastname: Villaseñor
authors.forename: R
authors.initials: R
authors.lastname: Fletterick
authors.forename: E
authors.initials: E
authors.lastname: Sigal
authors.forename: M F
authors.initials: MF
authors.lastname: Browner
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000378:metabolism; D016718:Arachidonic Acid; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D008049:Lipase / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D018996:Myelin P2 Protein / Q000737:chemistry / Q000378:metabolism; D009363:Neoplasm Proteins; D017433:Protein Structure, Secondary; D011817:Rabbits; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D016718:Arachidonic Acid; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D008049:Lipase