title: Molecular modeling studies on nucleoside hydrolase from the biological warfare agent Brucella suis.
abstract: Brucella suis is a dangerous biological warfare agent already used for military purposes. This bacteria cause brucellosis, a zoonosis highly infective and difficult to fight. An important selective target for chemotherapy against this disease is nucleoside hydrolase (NH), an enzyme still not found in mammals. We present here the first three-dimensional structure of B. suis NH (BsNH) and propose this enzyme as a molecular target to the drug design in the fight against brucellosis. In addition, we performed molecular docking studies, aiming to analyze the three-dimensional positioning of nine known inhibitors of Chritidia fasciculata NH (CfNH) in the active sites of BsNH and CfNH. We also analyzed the main interactions of some of these compounds inside the active site of BsNH and the relevant factors to biological activity. These results, together with further molecular dynamics (MD) simulations, pointed out to the most promising compound as lead for the design of potential inhibitors of BsNH. Most of the docking and MD results corroborated to each other and the docking results also suggested a good correlation with experimental data.
authors.affiliation: Chemistry Department, Federal University of Lavras - Campus Universitário - UFLA, Lavras, Brazil.
authors.forename: Daiana T
authors.initials: DT
authors.lastname: Mancini
authors.forename: Karina S
authors.initials: KS
authors.lastname: Matos
authors.forename: Elaine F F
authors.initials: EF
authors.lastname: da Cunha
authors.forename: Tamiris M
authors.initials: TM
authors.lastname: Assis
authors.forename: Ana P
authors.initials: AP
authors.lastname: Guimarães
authors.forename: Tanos C C
authors.initials: TC
authors.lastname: França
authors.forename: Teodorico C
authors.initials: TC
authors.lastname: Ramalho
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D054045:Biological Warfare Agents; D041021:Brucella suis / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics; D006860:Hydrogen Bonding; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D015203:Reproducibility of Results; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D054045:Biological Warfare Agents; D004791:Enzyme Inhibitors; D009699:N-Glycosyl Hydrolases