title: Crystal structure of YegS, a homologue to the mammalian diacylglycerol kinases, reveals a novel regulatory metal binding site.
abstract: The human lipid kinase family controls cell proliferation, differentiation, and tumorigenesis and includes diacylglycerol kinases, sphingosine kinases, and ceramide kinases. YegS is an Escherichia coli protein with significant sequence homology to the catalytic domain of the human lipid kinases. We have solved the crystal structure of YegS and shown that it is a lipid kinase with phosphatidylglycerol kinase activity. The crystal structure reveals a two-domain protein with significant structural similarity to a family of NAD kinases. The active site is located in the interdomain cleft formed by four conserved sequence motifs. Surprisingly, the structure reveals a novel metal binding site composed of residues conserved in most lipid kinases.
authors.affiliation: Division of Biophysics, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: H M Amin
authors.initials: HM
authors.lastname: Bakali
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Herman
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Amélie A
authors.initials: AA
authors.lastname: Kelly
authors.forename: Ake
authors.initials: A
authors.lastname: Wieslander
authors.forename: B Martin
authors.initials: BM
authors.lastname: Hallberg
authors.forename: Pär
authors.initials: P
authors.lastname: Nordlund
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D018360:Crystallography, X-Ray; D019852:Diacylglycerol Kinase / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: D029968:Escherichia coli Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase; C021844:NAD kinase