Structural highlights
Publication Abstract from PubMed
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.
Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA.,Hartkoorn RC, Pojer F, Read JA, Gingell H, Neres J, Horlacher OP, Altmann KH, Cole ST Nat Chem Biol. 2013 Dec 1. doi: 10.1038/nchembio.1405. PMID:24292073[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hartkoorn RC, Pojer F, Read JA, Gingell H, Neres J, Horlacher OP, Altmann KH, Cole ST. Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA. Nat Chem Biol. 2013 Dec 1. doi: 10.1038/nchembio.1405. PMID:24292073 doi:https://dx.doi.org/10.1038/nchembio.1405
