title: Structural basis for the rational design of new anti-Brucella agents: the crystal structure of the C366S mutant of L-histidinol dehydrogenase from Brucella suis.
abstract: L-Histidinol dehydrogenase from Brucella suis (BsHDH) is an enzyme involved in the histidine biosynthesis pathway which is absent in mammals, thus representing a very interesting target for the development of anti-Brucella agents. In this paper we report the crystallographic structure of a mutated form of BsHDH both in its unbound form and in complex with a nanomolar inhibitor. These studies provide the first structural background for the rational design of potent HDH inhibitors, thus offering new hints for clinical applications.
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: D'ambrosio
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France; Centre d'Etudes d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR 5236 CNRS-UM1-UM2, 1919 Route de Mende, 34293 Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Nina A
authors.initials: NA
authors.lastname: Dathan
authors.affiliation: Centre d'Etudes d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR 5236 CNRS-UM1-UM2, 1919 Route de Mende, 34293 Montpellier, France.
authors.forename: Safia
authors.initials: S
authors.lastname: Ouahrani-Bettache
authors.affiliation: Centre d'Etudes d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR 5236 CNRS-UM1-UM2, 1919 Route de Mende, 34293 Montpellier, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Köhler
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Ascione
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Napoli, Italy. Electronic address: marmonti@unina.it.
authors.forename: Simona Maria
authors.initials: SM
authors.lastname: Monti
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Napoli, Italy. Electronic address: gdesimon@unina.it.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Simone
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D041021:Brucella suis / Q000737:chemistry* / Q000201:enzymology; D002074:Butanones / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D015870:Gene Expression; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C000591053:3-amino-4-(1H-imidazol-5-yl)-1-(4-(phenylmethoxy)phenyl)butan-2-one; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002074:Butanones; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011994:Recombinant Proteins; D006639:Histidine; D000429:Alcohol Oxidoreductases; C021358:histidinol dehydrogenase
keywords: Brucella suis; Drug design; Inhibitor; X-ray crystallography; l-Histidinol dehydrogenase