title: Discovery of the first SecA inhibitors using structure-based virtual screening.
abstract: Bacterial protein secretion is a critical and complex process. The Sec machinery provides a major pathway for protein translocation across and integration into the cellular membrane in bacteria. Small molecule probes that perturb the functions of individual member proteins within the Sec machinery will be very important research tools as well as leads for future antimicrobial agent development. Herein we describe the discovery of inhibitors, through virtual screening, that specifically act on SecA ATPase, which is a critical member of the Sec system. These are the very first inhibitors reported for intrinsic SecA ATPase.
authors.affiliation: Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Campus Box 4098, Atlanta, GA 30302-4098, USA.
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Huang
authors.forename: Phang C
authors.initials: PC
authors.lastname: Tai
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D000069816:SEC Translocation Channels; D000081416:SecA Proteins; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; D054852:Small Molecule Libraries; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins