Structural studies of Mycobacterium tuberculosis DprE1 interacting with its inhabitors

The flavoenzyme DprEl catalyses a crucial step in arabinan production for cell wall biosynthesis in Mycobacterium tuberculosis and is a highly vulnerable drug target. It was first discovered using benzothiazinones (BTZ): exquisitely potent bactericidal agents that are being developed as drugs to treat tuberculosis. Subsequently, many compounds with diverse scaffolds were found to act as either covalent or noncovalent DprEl inhibitors. Covalent inhibitors, like the BTZ, are all nitroaromatic compounds that serve as suicide substrates after DprEl-mediated nitroreduction. Here, we describe how high resolution structures of DprEl, alone and in complex with various ligands, explain enzyme activity and inhibition.


Published in:
Drug Discovery Today, 22, 3, 526-533
Year:
2017
Publisher:
Oxford, Elsevier Sci Ltd
ISSN:
1359-6446
Laboratories:




 Record created 2017-05-01, last modified 2018-03-17


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