title: Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase complexed with cofactors: implications of a flexible loop movement upon substrate binding.
abstract: The key enzyme in the nonmevalonate pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), has been shown to be an effective target of antimalarial drugs. Here we report the crystal structure of DXR complexed with NADPH and a sulfate ion from Escherichia coli at 2.2 A resolution. The structure showed the presence of an extra domain, which is absent from other NADPH-dependent oxidoreductases, in addition to the conformation of catalytic residues and the substrate binding site. A flexible loop covering the substrate binding site plays an important role in the enzymatic reaction and the determination of substrate specificity.
authors.affiliation: Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan. yshun@nodai.ac.jp
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yajima
authors.forename: Takamasa
authors.initials: T
authors.lastname: Nonaka
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kuzuyama
authors.forename: Haruo
authors.initials: H
authors.lastname: Seto
authors.forename: Kanju
authors.initials: K
authors.lastname: Ohsawa
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain / Q000502:physiology; D003461:Crystallography; D004896:Erythritol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D009249:NADP / Q000737:chemistry* / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D010428:Pentosephosphates / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D013403:Sugar Phosphates / Q000737:chemistry / Q000378:metabolism
chemical_list: C109460:1-deoxylulose 5-phosphate; C114232:2-C-methylerythritol 4-phosphate; D009097:Multienzyme Complexes; D010428:Pentosephosphates; D013403:Sugar Phosphates; D009249:NADP; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases; D004896:Erythritol