Design of Potential Bisubstrate Inhibitors against Mycobacterium tuberculosis (Mtb) 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (Dxr)-Evidence of a Novel Binding Mode.

@article{Jose2013DesignOP,
  title={Design of Potential Bisubstrate Inhibitors against Mycobacterium tuberculosis (Mtb) 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (Dxr)-Evidence of a Novel Binding Mode.},
  author={G{\'e}raldine San Jose and Emily R. Jackson and Eugene Uh and Chinchu Johny and Amanda Haymond and Lindsay Lundberg and Chelsea Pinkham and Kylene Kehn-Hall and Helena I M Boshoff and Robin D. Couch and Cynthia S Dowd},
  journal={MedChemComm},
  year={2013},
  volume={4 7},
  pages={1099-1104}
}
In most bacteria, the nonmevalonate pathway is used to synthesize isoprene units. Dxr, the second step in the pathway, catalyzes the NADPH-dependent reductive isomerization of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol-4-phosphate (MEP). Dxr is inhibited by natural products fosmidomycin and FR900098, which bind in the DXP binding site. These compounds, while potent inhibitors of Dxr, lack whole cell activity against Mycobacterium tuberculosis (Mtb) due to their polarity… CONTINUE READING