Pyridomycin bridges the NADH- and substratebinding pockets of the enoyl reductase InhA

Pyridomycin, a natural product with potent antituberculosis activity, inhibits a major drug target, the InhA enoyl reductase. Here, we unveil the co-crystal structure and unique ability of pyridomycin to block both the NADH cofactor- and lipid substrate-binding pockets of InhA. This is to our knowledge a first-of-a-kind binding mode that discloses a new means of InhA inhibition. Proof-of-principle studies show how structure-assisted drug design can improve the activity of new pyridomycin derivatives.


Published in:
Nature Chemical Biology, 10, 2, 96-98
Year:
2014
Publisher:
New York, Nature Publishing Group
ISSN:
1552-4450
Laboratories:




 Record created 2014-04-02, last modified 2018-03-17


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