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3b4y

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Template:STRUCTURE 3b4y

Contents

FGD1 (Rv0407) from Mycobacterium tuberculosis

Template:ABSTRACT PUBMED 18434308

Function

[P96253_MYCTU] Catalyzes the coenzyme F420-dependent oxidation of glucose 6-phosphate to 6-phosphogluconolactone. Is essential for the bioreductive activation of the prodrug PA-824 (nitroimidazo-oxazine) developed for anti-tuberculosis therapy against both replicating and persistent bacteria. It does not interact directly with PA-824 but, rather, provides reduced F420 to an accessory protein (Rv3547), which in turn activates PA-824. Also probably has a role in resistance to oxidative stress, via its consumption of G6P that serves as a source of reducing power to combat oxidative stress in mycobacteria.[1][2]

About this Structure

3b4y is a 2 chain structure with sequence from Mycobacterium tuberculosis h37rv. Full crystallographic information is available from OCA.

Reference

  • Bashiri G, Squire CJ, Moreland NJ, Baker EN. Crystal structures of F420-dependent glucose-6-phosphate dehydrogenase FGD1 involved in the activation of the anti-tuberculosis drug candidate PA-824 reveal the basis of coenzyme and substrate binding. J Biol Chem. 2008 Jun 20;283(25):17531-41. Epub 2008 Apr 22. PMID:18434308 doi:10.1074/jbc.M801854200
  1. ↑ Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, Langhorne MH, Anderson SW, Towell JA, Yuan Y, McMurray DN, Kreiswirth BN, Barry CE, Baker WR. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature. 2000 Jun 22;405(6789):962-6. PMID:10879539 doi:10.1038/35016103
  2. ↑ Bashiri G, Squire CJ, Moreland NJ, Baker EN. Crystal structures of F420-dependent glucose-6-phosphate dehydrogenase FGD1 involved in the activation of the anti-tuberculosis drug candidate PA-824 reveal the basis of coenzyme and substrate binding. J Biol Chem. 2008 Jun 20;283(25):17531-41. Epub 2008 Apr 22. PMID:18434308 doi:10.1074/jbc.M801854200

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