title: Novel concept of enzyme selective nicotinamide adenine dinucleotide (NAD)-modified inhibitors based on enzyme taxonomy from the diphosphate conformation of NAD.
abstract: The dihedral angle θ of the diphosphate part of NAD(P) were investigated to distinguish the differences in the binding-conformation of NAD(P) to enzymes and to create an enzyme taxonomy. Furthermore, new inhibitors with fixed dihedral angles showed that enzymes could recognize the differences in the dihedral angle θ. We suggest the taxonomy and the dihedral angle θ are important values for chemists to consider when designing inhibitors and drugs that target enzymes.
authors.affiliation: School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan; Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. Electronic address: mfujii@iuhw.ac.jp.
authors.forename: Mikio
authors.initials: M
authors.lastname: Fujii
authors.affiliation: School of Pharmacy, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, Kanagawa 245-0066, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Shui
authors.initials: S
authors.lastname: Iida
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kato
authors.affiliation: School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Ono
mesh_terms: D000818:Animals; D002645:Chickens; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007700:Kinetics; D008968:Molecular Conformation; D009243:NAD / Q000031:analogs & derivatives* / Q000737:chemistry*; D064430:NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000145:classification; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000737:chemistry; D012441:Saccharomyces cerevisiae; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D013844:Thiazoles; D009243:NAD; D010088:Oxidoreductases; D064430:NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; D017853:Phosphotransferases (Alcohol Group Acceptor); C021844:NAD kinase
keywords: Conformation; Diphosphate; Enzyme selective inhibitor; Enzyme taxonomy; NAD(P)