Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 132, Issue 8, Pages 2518-+Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja910361r
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- NIH [AI081059]
- NSF
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The outer membrane of Gram-negative bacteria contains an outer leaflet composed of lipopolysaccharide (LPS) that is transported to this location by a pathway that is essential for viability. It has been suggested that inhibitors of this pathway Could be useful antibiotics. Herein we reconstitute the activity of the ATPase component (LptB) of the ABC transporter that initiates LPS transport and assembly. We developed a high-throughput assay and screened a library of kinase inhibitors against LptB. We identified two classes of ATP-competitive inhibitors. These are the first inhibitors of the ATPase component of any bacterial ABC transporter. The small-molecule inhibitors will be very useful tools for further biochemical Studies of the proteins involved in LPS transport and assembly.
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