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Comparative Study
. 2014 Feb;10(2):96-8.
doi: 10.1038/nchembio.1405. Epub 2013 Dec 1.

Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA

Ruben C Hartkoorn  1 , Florence Pojer  1 , Jon A Read  2 , Helen Gingell  2 , João Neres  1 , Oliver P Horlacher  3 , Karl-Heinz Altmann  3 , Stewart T Cole  1
Affiliations
Comparative Study

Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA

Ruben C Hartkoorn et al. Nat Chem Biol. 2014 Feb.

Abstract

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.

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References

    1. Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42 - PubMed
    1. Biochemistry. 1995 May 9;34(18):6003-13 - PubMed
    1. ACS Chem Biol. 2006 Feb 17;1(1):43-53 - PubMed
    1. J Med Chem. 2006 Oct 19;49(21):6308-23 - PubMed
    1. ACS Med Chem Lett. 2012 Dec 18;4(2):264-8 - PubMed

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