Identification of small molecule inhibitors against SecA of Candidatus Liberibacter asiaticus by structure based design.
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.
Citrus Research & Education Center, Department of Microbiology and Cell Science, University of Florida, 700 Experiment Station Rd., Lake Alfred, FL 33850, USA.
Nagaraju
N
Akula
Pankaj
P
Trivedi
Frank Q
FQ
Han
Nian
N
Wang
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D016960:Agrobacterium tumefaciens / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D015195:Drug Design; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D012230:Rhizobiaceae / Q000187:drug effects / Q000201:enzymology*; D000069816:SEC Translocation Channels; D000081416:SecA Proteins; D017386:Sequence Homology, Amino Acid; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; D054852:Small Molecule Libraries; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins