title: Crystal Structures of a Hyperthermophilic Archaeal Homoserine Dehydrogenase Suggest a Novel Cofactor Binding Mode for Oxidoreductases.
abstract: NAD(P)-dependent dehydrogenases differ according to their coenzyme preference: some prefer NAD, others NADP, and still others exhibit dual cofactor specificity. The structure of a newly identified archaeal homoserine dehydrogenase showed this enzyme to have a strong preference for NADP. However, NADP did not act as a cofactor with this enzyme, but as a strong inhibitor of NAD-dependent homoserine oxidation. Structural analysis and site-directed mutagenesis showed that the large number of interactions between the cofactor and the enzyme are responsible for the lack of reactivity of the enzyme towards NADP. This observation suggests this enzyme exhibits a new variation on cofactor binding to a dehydrogenase: very strong NADP binding that acts as an obstacle to NAD(P)-dependent dehydrogenase catalytic activity.
authors.affiliation: Department of Applied Biological Science, Faculty of Agriculture, Kagawa University, Ikenobe 2393, Miki-cho, Kagawa 761-0795, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Hayashi
authors.affiliation: Department of Applied Biological Science, Faculty of Agriculture, Kagawa University, Ikenobe 2393, Miki-cho, Kagawa 761-0795, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka 560-0043, Japan.
authors.forename: Kwang
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Bioscience, School of Agriculture, Tokai University, Aso, Kumamoto, 869-1404, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoneda
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Amagasaki 661-0974, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawarabayasi
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Osaka Institute of Technology, 5-16-1, Ohmiya, Asahi-ku, Osaka, 535-8585, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ohshima
authors.affiliation: Department of Applied Biological Science, Faculty of Agriculture, Kagawa University, Ikenobe 2393, Miki-cho, Kagawa 761-0795, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sakuraba
mesh_terms: D000595:Amino Acid Sequence; D001105:Archaea / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D006715:Homoserine Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009249:NADP / Q000737:chemistry / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D009249:NADP; D010088:Oxidoreductases; D006715:Homoserine Dehydrogenase