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DprE1 Is a Vulnerable Tuberculosis Drug Target Due to Its Cell Wall Localization.
Brecik, Miroslav; Centárová, Ivana; Mukherjee, Raju; Kolly, Gaëlle S; Huszár, Stanislav; Bobovská, Adela; Kilacsková, Emöke; Mokosová, Veronika; Svetlíková, Zuzana; Sarkan, Michal; Neres, João; Korduláková, Jana; Cole, Stewart T; Mikusová, Katarína.
Affiliation
  • Brecik M; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Centárová I; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Mukherjee R; ‡Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • Kolly GS; ‡Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • Huszár S; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Bobovská A; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Kilacsková E; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Mokosová V; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Svetlíková Z; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Sarkan M; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Neres J; ‡Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • Korduláková J; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
  • Cole ST; ‡Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • Mikusová K; †Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia.
ACS Chem Biol ; 10(7): 1631-6, 2015 Jul 17.
Article in En | MEDLINE | ID: mdl-25906160
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.
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Full text: 1 Collection: 01-internacional Health context: 2_ODS3 / 3_ND Database: MEDLINE Main subject: Bacterial Proteins / Tuberculosis / Cell Wall / Alcohol Oxidoreductases / Mycobacterium tuberculosis / Antitubercular Agents Limits: Humans Language: En Journal: ACS Chem Biol Year: 2015 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Health context: 2_ODS3 / 3_ND Database: MEDLINE Main subject: Bacterial Proteins / Tuberculosis / Cell Wall / Alcohol Oxidoreductases / Mycobacterium tuberculosis / Antitubercular Agents Limits: Humans Language: En Journal: ACS Chem Biol Year: 2015 Document type: Article