Decaprenylphosphoryl-beta-D-ribose 2-oxidase (DprE1)

Decaprenylphosphoryl-beta-D-ribose 2-oxidase, commonly known as DprE1, is an essential FAD-dependent enzyme in Mycobacterium tuberculosis (UniProt: P9WGI1). It catalyzes the first step in the epimerization of decaprenylphosphoryl-ribose (DPR) to decaprenylphosphoryl-arabinose (DPA), which is the sole donor of arabinosyl residues for the synthesis of the mycobacterial cell wall components arabinogalactan and lipoarabinomannan (Makarov et al., Science, 2009). Because DPA is critical for maintaining the structural integrity of the cell wall, DprE1 is a highly validated target for the development of new anti-tuberculosis agents (Piton et al., Drug Discovery Today, 2017). Several classes of inhibitors, including benzothiazinones like BTZ043 and macozinone, have been developed to target this enzyme, often acting through covalent binding to a conserved cysteine residue (Cys387) in the active site (Bhat et al., Journal of Medicinal Chemistry, 2013). Inhibition of DprE1 leads to cell wall lysis and bacterial death, making it a potent target for treating both drug-sensitive and multi-drug-resistant tuberculosis (Hariguchi et al., Scientific Reports, 2020). The enzyme's location in the periplasmic space and the absence of a human homolog make it an attractive target for small-molecule drug discovery.

Other names

DprE1Rv3790Decaprenylphosphoryl-D-ribose oxidaseDecaprenylphosphoryl-beta-D-ribofuranose 2-oxidaseDPR oxidase

Inhibition of the DprE1 enzyme, which blocks the synthesis of decaprenylphosphoryl-arabinose (DPA), an essential precursor for mycobacterial cell wall assembly, leading to bacterial cell lysis.