title: Crystal structure of a fructokinase homolog from Halothermothrix orenii.
abstract: Fructokinase (FRK; EC 2.7.1.4) catalyzes the phosphorylation of d-fructose to d-fructose 6-phosphate (F6P). This irreversible and near rate-limiting step is a central and regulatory process in plants and bacteria, which channels fructose into a metabolically active state for glycolysis. Towards understanding the mechanism of FRK, here we report the crystal structure of a FRK homolog from a thermohalophilic bacterium Halothermothrixorenii (Hore_18220 in sequence databases). The structure of the Hore_18220 protein reveals a catalytic domain with a Rossmann-like fold and a beta-sheet "lid" for dimerization. Based on comparison of Hore_18220 to structures of related proteins, we propose its mechanism of action, in which the lid serves to regulate access to the substrate binding sites. Close relationship of Hore_18220 and plant FRK enzymes allows us to propose a model for the structure and function of FRKs.
authors.affiliation: Department of Biological Sciences, 14 Science Drive 4, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Teck Khiang
authors.initials: TK
authors.lastname: Chua
authors.forename: J
authors.initials: J
authors.lastname: Seetharaman
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Kasprzak
authors.forename: Cherlyn
authors.initials: C
authors.lastname: Ng
authors.forename: Bharat K C
authors.initials: BK
authors.lastname: Patel
authors.forename: Christopher
authors.initials: C
authors.lastname: Love
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
authors.forename: J
authors.initials: J
authors.lastname: Sivaraman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D003013:Clostridium / Q000201:enzymology*; D005631:Fructokinases / Q000737:chemistry* / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D005632:Fructose; D000255:Adenosine Triphosphate; D005631:Fructokinases; C046173:fructokinase