Molecular modeling studies on nucleoside hydrolase from the biological warfare agent Brucella suis

• Published in: Journal of biomolecular structure & dynamics Vol. 30; no. 1; pp. 125 - 136
• Main Authors: Mancini, Daiana T., Matos, Karina S., da Cunha, Elaine F.F., Assis, Tamiris M., Guimarães, Ana P., França, Tanos C.C., Ramalho, Teodorico C.
• Format: Journal Article
• Language: English
• Published: England Routledge 01.01.2012
• Subjects: Amino Acid Sequence; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Biological Warfare Agents; Brucella suis; Brucella suis - chemistry; Brucella suis - drug effects; Brucella suis - enzymology; Brucellosis; Catalytic Domain; Chemotherapy; Data processing; docking; Drug development; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacokinetics; Enzymes; homology modeling; Hydrogen Bonding; hydrolase; Kinetics; molecular dynamics; Molecular Dynamics Simulation; Molecular modelling; Molecular Sequence Data; N-Glycosyl Hydrolases - antagonists & inhibitors; N-Glycosyl Hydrolases - chemistry; N-Glycosyl Hydrolases - metabolism; nucleoside hydrolase; nucleosides; Protein Binding; Reproducibility of Results; Sequence Alignment
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2012.674293

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.