Abstract
The flavo-enzyme DprE1 catalyzes a key epimerization step in the decaprenyl-phosphoryl d-arabinose (DPA) pathway, which is essential for mycobacterial cell wall biogenesis and targeted by several new tuberculosis drug candidates. Here, using differential radiolabeling with DPA precursors and high-resolution fluorescence microscopy, we disclose the unexpected extracytoplasmic localization of DprE1 and periplasmic synthesis of DPA. Collectively, this explains the vulnerability of DprE1 and the remarkable potency of the best inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alcohol Oxidoreductases / analysis*
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Alcohol Oxidoreductases / metabolism*
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Antitubercular Agents / pharmacology*
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Bacterial Proteins / analysis*
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Bacterial Proteins / metabolism*
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Cell Wall / drug effects
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Cell Wall / metabolism*
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Humans
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Mycobacterium tuberculosis / cytology*
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / enzymology*
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Tuberculosis / drug therapy
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Tuberculosis / microbiology*
Substances
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Antitubercular Agents
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Bacterial Proteins
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Alcohol Oxidoreductases
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DprE1 protein, Mycobacterium tuberculosis