Phosphoribosyltransferase (PRTase)

Phosphoribosyltransferases (PRTases) represent a functionally diverse superfamily of enzymes that catalyze the transfer of a 5-phosphoribosyl group from 5-phosphoribosyl-1-pyrophosphate (PRPP) to various nitrogenous bases [7, 14, 15]. This reaction is a cornerstone of cellular metabolism, facilitating the de novo synthesis and salvage of purine and pyrimidine nucleotides, the production of the essential cofactor NAD+, and the biosynthesis of certain amino acids [8, 12, 16]. Key members of this family include Nicotinamide phosphoribosyltransferase (NAMPT), which regulates NAD+ levels and is a major therapeutic target in oncology and inflammatory diseases, and Hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which is critical for purine recycling and is linked to Lesch-Nyhan syndrome when deficient [1, 6, 20]. In pharmacological contexts, PRTases are targeted both for direct inhibition, such as using NAMPT inhibitors (e.g., daporinad) to induce metabolic collapse in cancer cells, and for the bioactivation of antimetabolite prodrugs like 5-fluorouracil or 6-mercaptopurine [3, 4, 10, 18]. Furthermore, because many pathogens rely on specific PRTases for essential nucleotide salvage, these enzymes serve as important targets for the development of novel antimicrobial and antiparasitic agents [5, 13, 19].

Other names

PentosyltransferasePRTPhosphoribosyl transferasePRTase family

Inhibition of NAD+ salvage (targeting NAMPT), competitive inhibition of purine salvage (targeting HGPRT), or metabolic activation of antimetabolite prodrugs into cytotoxic nucleotides (targeting OPRT or HGPRT).