title: Ligand-induced changes in the conformation of 3-isopropylmalate dehydrogenase from Thermus thermophilus.
abstract: The structures of 3-isopropylmalate dehydrogenase (IPMDH) from Thermus thermophilus in complexes with its substrate, cofactor, and a cofactor analog were investigated by X-ray diffraction in a crystalline state and by small-angle X-ray scattering (SAXS) in solution. The structures at 2.8 A resolution of the complexes with the substrate, 3-isopropylmalate (IPM), and with an analog of NAD, ADP-ribose, were both very close to the structure of the free enzyme, which adopts an open conformation. However, the binding of a ligand induced a small conformational change near the binding site. This result contrasts with results for NADP(+)-bound and isocitrate-bound isocitrate dehydrogenase (ICDH) from Escherichia coli, which adopts a closed conformation. The SAXS analysis in solution clearly showed that IPMDH without a ligand adopts two distinct intermediate conformations, between the open and closed states, upon binding of NADH and IPM respectively, and adopts a fully closed conformation when in a ternary complex with NADH and IPM together.
authors.affiliation: Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama.
authors.forename: S
authors.initials: S
authors.lastname: Kadono
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
authors.forename: H
authors.initials: H
authors.lastname: Moriyama
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Oshima
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D050539:3-Isopropylmalate Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008024:Ligands; D008969:Molecular Sequence Data; D011487:Protein Conformation / Q000187:drug effects; D016415:Sequence Alignment; D016963:Thermus thermophilus / Q000201:enzymology*
chemical_list: D008024:Ligands; D000429:Alcohol Oxidoreductases; D050539:3-Isopropylmalate Dehydrogenase