SecA ATPase is a critical member of the Sec family, which is important in the translocation of membrane and secreted polypeptides/proteins in bacteria. Small molecule inhibitors can be very useful research tools as well as leads for future antimicrobial agent development. Based on previous virtual screening work, we optimized the structures of two hit compounds and obtained SecA ATPase inhibitors with IC(50) in the single digit micromolar range. These represent the first low micromolar synthetic inhibitors of bacterial SecA and will be very useful for mechanistic studies.
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| http://dx.doi.org/10.1016/j.bmc.2009.12.074 | DOI Listing |
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Screening a library of temperature-sensitive mutants to identify secretion factors in .
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Department of Microbiology, Howard Taylor Ricketts Laboratory, The University of Chicago, Chicago, Illinois, USA.
Protein secretion is an essential cell process in bacteria, required for cell envelope biogenesis, export of virulence factors, and acquisition of nutrients, among other important functions. In the Sec secretion pathway, signal peptide-bearing precursors are recognized by the SecA ATPase and pushed across the membrane through a translocon channel made of the proteins SecY, SecE, and SecG. The Sec pathway has been extensively studied in the model organism , but the Sec pathways of other bacteria such as the human pathogen differ in important ways from this model.
View Article and Find Full Text PDFProtein translocation across cellular membranes is an essential and nano-scale dynamic process. In the bacterial cytoplasmic membrane, the core proteins in this process are a membrane protein complex, SecYEG, corresponding to the eukaryotic Sec61 complex, and a cytoplasmic protein, SecA ATPase. Despite more than three decades of extensive research on Sec proteins, from genetic experiments to cutting-edge single-molecule analyses, no study has visually demonstrated protein translocation.
View Article and Find Full Text PDFPhysical mechanisms of the Sec machinery operation.
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Institute for Theoretical Physics, Johannes Kepler University Linz, Altenberger Strasse 69, A-4040 Linz, Austria.
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Department of Chemistry, University of Crete, Voutes, 70013, Heraklion, Greece.
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