Structural highlights
Function
FGD_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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ 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
- ↑ 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
