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

Decaprenylphosphoryl-beta-D-ribose 2'-oxidase, commonly known as DprE1, is an essential flavin adenine dinucleotide (FAD)-dependent enzyme in Mycobacterium tuberculosis that is critical for the synthesis of the mycobacterial cell wall [1.1.1, 1.3.1]. It catalyzes the first step in the epimerization of decaprenylphosphoryl-D-ribose (DPR) to decaprenylphosphoryl-D-arabinose (DPA), which serves as the sole donor of arabinosyl residues for the construction of the arabinan segments in arabinogalactan and lipoarabinomannan [1.1.2, 1.3.3]. Because DPA is a unique and vital component of the mycobacterial cell envelope and DprE1 has no human homologs, it is considered a highly attractive and validated therapeutic target for tuberculosis treatment [1.1.3, 1.2.4]. Several classes of small molecules, including benzothiazinones (e.g., BTZ043, Macozinone) and azaindoles, have been identified as potent DprE1 inhibitors that cause cell wall degradation and bacterial lysis [1.2.1, 1.4.1]. These drugs have demonstrated significant efficacy against both drug-sensitive and multidrug-resistant (MDR) strains of M. tuberculosis in clinical trials [1.2.2, 1.2.4]. The enzyme's accessibility in the periplasmic space further enhances its viability as a drug target, although the emergence of resistance through specific point mutations remains a clinical challenge [1.2.2, 1.4.3].

Other names

DprE1Rv3790Decaprenylphosphoryl-beta-D-ribose 2'-epimerase subunit 1FAD-dependent oxidoreductase DprE1

Inhibition of the DprE1 enzyme, which prevents the conversion of decaprenylphosphoryl-ribose to decaprenylphosphoryl-arabinose, thereby blocking the synthesis of essential cell wall components (arabinogalactan and lipoarabinomannan) and leading to bacterial cell lysis.