1. Identification of small molecule inhibitors against SecA of Candidatus Liberibacter asiaticus by structure based design.
- Author
-
Akula N, Trivedi P, Han FQ, and Wang N
- Subjects
- Adenosine Triphosphatases chemistry, Adenosine Triphosphatases metabolism, Adenosine Triphosphate metabolism, Agrobacterium tumefaciens drug effects, Anti-Bacterial Agents metabolism, Bacterial Proteins chemistry, Bacterial Proteins metabolism, Binding Sites, Membrane Transport Proteins chemistry, Membrane Transport Proteins metabolism, Molecular Docking Simulation, Protein Conformation, Rhizobiaceae drug effects, SEC Translocation Channels, SecA Proteins, Sequence Homology, Amino Acid, Small Molecule Libraries metabolism, Adenosine Triphosphatases antagonists & inhibitors, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Bacterial Proteins antagonists & inhibitors, Drug Design, Rhizobiaceae enzymology, Small Molecule Libraries chemistry, Small Molecule Libraries pharmacology
- Abstract
Huanglongbing is the most devastating disease of citrus caused by Candidatus Liberibacter asiaticus (Las). In the present study, we report the discovery of novel small molecule inhibitors against SecA ATPase of Las by using structure based design methods. We built the homology model of SecA protein structure of Las based on the SecA of Escherichia coli. The model was used for in-silico screening of commercially available compounds from ZINC database. Using the glide flexible molecular docking method, twenty structures were chosen for in vitro studies. Five compounds were found to inhibit the ATPase activity of SecA of Las at nano molar concentrations and showed antimicrobial activities against Agrobacterium tumefaciens with MBC ranging from 128 to 256 μg/mL. These compounds appear to be suitable as lead compounds for further development of antimicrobial compounds against Las., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF