Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1)

Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) is a highly conserved flavoenzyme in mycobacteria, essential for the biosynthesis of key cell wall components such as arabinogalactan and lipoarabinomannan[1][2][4]. DprE1 catalyzes the FAD-dependent oxidation of decaprenylphosphoryl-D-ribose to decaprenylphosphoryl-2-ketoribose, with the latter subsequently reduced by DprE2 to form decaprenylphosphoryl arabinose, a substrate for cell wall construction[3][4]. Structural studies reveal DprE1 is membrane-associated and undergoes conformational changes upon ligand binding[1]. With its critical role, DprE1 is intensively targeted for tuberculosis drug discovery, and numerous small molecule inhibitors have been developed—some in clinical evaluation[2][4]. The enzyme’s druggability, potential for resistance, and central role in cell survival make it a focal point for novel therapeutics.

Other names

Mycobacterial cell wall synthesis enzyme DprE1Decaprenylphosphoryl-β-D-ribose epimerase 1DprE1 flavoenzyme

Covalent inhibition of the active site (by some inhibitors such as benzothiazinones) - Noncovalent active site blockade (by other scaffolds, e.g., hydantoin derivatives, quinoxalines) - Inhibition of cell wall biosynthesis, leading to mycobacterial cell death