ATP phosphoribosyltransferase (ATP-PRT)

ATP phosphoribosyltransferase (ATP-PRT) is a critical enzyme that catalyzes the first committed step in the biosynthesis of the essential amino acid L-histidine. It facilitates the condensation of adenosine triphosphate (ATP) and 5-phospho-D-ribosyl-1-pyrophosphate (PRPP) to produce N'-5'-phosphoribosyl-ATP (UniProt: P9WNB1). This enzyme is found in bacteria, archaea, and plants but is entirely absent in mammals, making it an ideal target for antimicrobial drug development (PubMed: 26150465). In pathogens like Mycobacterium tuberculosis, ATP-PRT is essential for growth and virulence, and its inhibition leads to histidine starvation and metabolic arrest. The enzyme exists in two distinct forms—a long form (HisG_L) and a short form (HisG_S)—and is naturally regulated by allosteric feedback inhibition by L-histidine (PubMed: 30102015). Therapeutic strategies focus on developing small-molecule inhibitors that mimic this feedback inhibition or block the active site to treat infections without affecting human host cells.

Other names

Phosphoribosyl-ATP pyrophosphorylaseATP-PRTaseHisGEC 2.4.2.17

Inhibition of the rate-limiting first step of the L-histidine biosynthetic pathway, leading to histidine starvation and bacterial growth arrest.