Hartkoorn, Ruben C.Pojer, FlorenceRead, Jon A.Gingell, HelenNeres, JoaoHorlacher, Oliver P.Altmann, Karl-HeinzCole, Stewart T.2014-04-022014-04-022014-04-02201410.1038/nchembio.1405https://infoscience.epfl.ch/handle/20.500.14299/102448WOS:000330751600006Pyridomycin, 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.text::journal::journal article::research article