Decaprenylphosphoryl-β-D-ribose 2′-epimerase 1 (DprE1)

Decaprenylphosphoryl-β-D-ribose 2′-epimerase 1 (DprE1) is an essential FAD-dependent oxidoreductase in Mycobacterium tuberculosis that catalyzes the first step in the epimerization of decaprenylphosphoryl-β-D-ribose to decaprenylphosphoryl arabinose, a precursor for cell wall arabinan and lipoarabinomannan. DprE1 operates as part of a membrane-associated complex with DprE2 and is highly conserved among mycobacteria. The enzyme is a key vulnerability exploited in anti-tuberculosis drug development; covalent inhibitors such as BTZ043 and non-covalent inhibitors like 2-carboxyquinoxalines block its activity, preventing cell wall biosynthesis and leading to bacterial cell death. DprE1 is regarded as a highly validated and promising drug target for tuberculosis and potentially for other mycobacterial infections[1][2][3][4][5][6][8].

Other names

Decaprenylphosphoryl-β-D-ribose oxidaseDecaprenylphosphoryl-D-ribose 2-epimeraseRv3790 (gene name in Mycobacterium tuberculosis)

Covalent and non-covalent inhibition of DprE1 enzymatic activity, blocking cell wall arabinan biosynthesis and causing cell death in mycobacteria[1][3][4][5][6].