Mechanism and Catalytic Site Atlas

Quinolinic acid phosphoribosyltransferase from Mycobacterium Tuberculosis (Mt-QAPRTase) is required for the de novo biosynthesis of NAD in both prokaryotes and eukaryotes (equivalent enzyme). The enzyme catalyses the reaction between quinolinic acid (QA) and 5-phosphoribosyl-1-pyrophosphate (PRPP), to yield nicotinic acid mononucleotide (NAMN), pyrophosphate and CO₂, the latter resulting from decarboxylation at position 2 of the quinolinate ring.

QAPRTase has been grouped with other phosphoribosyltransferases, (PRTases) that catalyse chemically similar phosphoribosyl transfer reactions using the substrate PRPP. The PRTases are involved in de novo and salvage reactions of nucleotide synthesis, as well as in histidine and tryptophan biosynthesis [PMID:9016724]. To date, crystal structures have been determined for several PRTase enzymes and all show a common 'PRTase fold' (the 'type I' fold) composed of a central beta sheet, of five beta strands, surrounded by alpha helices. The fold contains a common recognition motif of thirteen residues which is critical for PRPP binding and catalysis. However, as type II enzymes like Mt-QAPRTase lack the type I PRPP-binding motif and have TIM barrel-like structure, it becomes possible that there might be at least two different types of PRTase fold [PMID:9016724]. Despite their structural differences, it has been suggested TI and TII indeed still have the same catalytic mechanism but more work is needed to understand this fully.