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ACS Chem Biol. 2015 Jul 17;10(7):1631-6. doi: 10.1021/acschembio.5b00237. Epub 2015 Apr 29.

DprE1 Is a Vulnerable Tuberculosis Drug Target Due to Its Cell Wall Localization.

Author information

1
†Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
2
‡Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.

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.

PMID:
25906160
DOI:
10.1021/acschembio.5b00237
[Indexed for MEDLINE]

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