title: Discovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design.
abstract: Candidatus Liberibacter asiaticus is the causal agent of Huanglongbing (HLB) disease of citrus. Current management practices have not been able to control HLB and stop the spread of HLB. The current study is focused on screening small molecule inhibitors against SecA protein of Ca. L. asiaticus. Homology modeling, structure based virtual screening and molecular docking methods have been used to find the novel inhibitory compounds against SecA activity at ATP binding region. At 20μm 17 compounds showed >50% inhibition and four compounds had more than 65% inhibition. The most active compound has IC(50) value of 2.5μM. The differences between the activities of the compounds are explained by their inter-molecular interactions at ATP binding site.
authors.affiliation: Citrus Research & Education Center, Department of Microbiology and Cell Science, University of Florida, 700 Experiment Station Rd., Lake Alfred, FL 33850, USA.
authors.forename: Nagaraju
authors.initials: N
authors.lastname: Akula
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Frank Q
authors.initials: FQ
authors.lastname: Han
authors.forename: Nian
authors.initials: N
authors.lastname: Wang
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D026901:Membrane Transport Proteins / Q000378:metabolism; D012230:Rhizobiaceae / Q000378:metabolism*; D000069816:SEC Translocation Channels; D000081416:SecA Proteins; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; D054852:Small Molecule Libraries; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins