DprE1 Is a Vulnerable Tuberculosis Drug Target Due to Its Cell Wall Localization
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- 作者：Miroslav Brecik ; Ivana Cent谩rov谩 ; Raju Mukherjee ; Ga毛lle S. Kolly ; Stanislav Husz谩r ; Adela Bobovsk谩 ; Em枚ke Kilacskov谩 ; Veronika Moko拧ov谩 ; Zuzana Svetl铆kov谩 ; Michal 艩arkan ; Jo茫o Neres ; Jana Kordul谩kov谩 ; Stewart T. Cole ; Katar铆na Miku拧ov谩
- 刊名：ACS Chemical Biology
- 出版年：2015
- 出版时间：July 17, 2015
- 年：2015
- 卷：10
- 期：7
- 页码：1631-1636
- 全文大小：323K
- ISSN：1554-8937
文摘
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.