Phosphoribosyltransferases

Phosphoribosyltransferases (PRTases) are a diverse group of enzymes that catalyze the transfer of the 5-phosphoribosyl group from 5-phosphoribosyl-1-pyrophosphate (PRPP) to an acceptor molecule, typically a nitrogen or oxygen atom on a heterocyclic base, forming a nucleotide monophosphate and pyrophosphate. This reaction links PRPP to the bases in salvage pathways for purines and pyrimidines and to the biosynthesis of certain cofactors.

Representative members include adenine phosphoribosyltransferase (APRT), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), orotate phosphoribosyltransferase (OPRT), uracil phosphoribosyltransferase (UPRT), and xanthine phosphoribosyltransferase (XPRT); nicotinamide phosphoribosyltransferase (NAMPT) is involved in NAD biosynthesis. Substrates vary: APRT uses adenine to yield AMP; HGPRT uses hypoxanthine or guanine to yield IMP or GMP; OPRT uses orotate to OMP; UPRT uses uracil to UMP; XPRT uses xanthine to XMP; NAMPT uses nicotinamide to NMN. In all cases PRPP is the donor and pyrophosphate is released.

Physiological roles include salvage of free bases into nucleotides and, in mammals, salvage of NAD precursors. Defects in PRTases can have clinical consequences: HGPRT deficiency causes Lesch-Nyhan syndrome, while APRT deficiency can lead to 2,8-dihydroxyadenine stones. Because many PRTases are essential in pathogens and possess distinct active sites, they are targets for antimicrobial and anticancer agents, and structural studies aid inhibitor design.

Most PRTases are cytosolic enzymes with conserved motifs for PRPP binding and base orientation, yet they exhibit substantial substrate diversity across organisms.