title: Molecular properties of diacylglycerol kinase-epsilon in relation to function.
abstract: The epsilon isoform of mammalian diacylglycerol kinase (DGKϵ) is an enzyme that associates strongly with membranes and acts on a lipid substrate, diacylglycerol. The protein has one segment that is predicted to be a transmembrane helix, but appears to interconvert between a transmembrane helix and a re-entrant helix. Despite the hydrophobicity of this segment and the fact that the lipid substrate is also hydrophobic, removal of this hydrophobic segment by truncating the protein at the amino terminus has no effect on its enzymatic activity. The amino acid sequence of the catalytic segment of DGKϵ is highly homologous to that of a bacterial DGK, DgkB. This has allowed us to predict a conformation of DGKϵ based on the known crystal structure of DgkB. An important property of DGKϵ is that it is specific for diacylglycerol species containing an arachidonoyl group. The region of DGKϵ that interacts with this group is found within the accessory domain of the protein and not in the active site nor in the hydrophobic amino terminus. The nature of the acyl chain specificity of the enzyme indicates that DGKϵ is associated with the synthesis of phosphatidylinositol. Defects or deletion of the enzyme give rise to several disease states.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Jennings
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Sejal
authors.initials: S
authors.lastname: Doshi
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Kenneth
authors.initials: K
authors.lastname: D'Souza
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada. Electronic address: epand@mcmaster.ca.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Epand
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D019852:Diacylglycerol Kinase / Q000737:chemistry / Q000378:metabolism*; D004075:Diglycerides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010716:Phosphatidylinositols / Q000096:biosynthesis; D011487:Protein Conformation
chemical_list: D004075:Diglycerides; D010716:Phosphatidylinositols; C526464:DGKE protein, human; D019852:Diacylglycerol Kinase
keywords: Arachidonic acid; Diacylglycerol kinase; Lipid binding; Lipid substrate specificity