Enzyme - Nicotinate-nucleotide diphosphorylase (carboxylating)

Alternative Name(s)
  • Nicotinate-nucleotide pyrophosphorylase (carboxylating).
  • Quinolinate phosphoribosyltransferase (decarboxylating).

Catalytic Activity

CO2 + diphosphate + nicotinate beta-D-ribonucleotide = 5-phospho-alpha-D-ribose 1-diphosphate + 2 H(+) + quinolinate


There are no Cofactors for this Enzyme

Reaction Mechanisms

    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.

    Phosphoribosyl transfer has been proposed to proceed via a unimolecular nucleophilic substitution (SN1 reaction) involving an oxycarbonium-like intermediate. In a rate-limiting step, the pyrophosphate group of PRPP is protonated and cleaved to yield an oxycarbonium of ribosylphosphate. The formation of the anticipated intermediate may be facilitated by the electron-withdrawing power of the metal ions and the C3-exo pucker of the ribosyl ring. Subsequently, the nucleophilic N1 of QA combines with the oxycarbonium in a diffusion-controlled reaction to form quinolinic acid mononucleotide (QAMN) [PMID:9862811].
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Glu P9WJJ7 201 1qpr 200
    Lys P9WJJ7 140 1qpr 139
    Arg P9WJJ7 105 1qpr 104
    Lys P9WJJ7 172 1qpr 171
    Asp P9WJJ7 222 1qpr 221
    Step Components

    inferred reaction step, dephosphorylation, intermediate formation, heterolysis, intermediate terminated, bimolecular nucleophilic addition, rate-determining step, proton transfer, bond polarisation, overall reactant used, unimolecular elimination by the conjugate base, intermediate collapse, native state of enzyme is not regenerated, decarboxylation, overall product formed

    Step 1.

    Glu201 deprotonates the 3-OH of the ribose substrate.

    Step 2.

    The ribose intermediate undergoes an elimination reaction, with concomitant deprotonation of an unidentified base, represented here as a hydronium ion.

    Step 3.

    The nitrogen of the pyridine initiates a nucleophilic attack on the ribose in an addition reaction.

    Step 4.

    The pyridine intermediate decarboxylates with concomitant deprotonation of Lys172. Proton transfer to nicotinamide carbon is inferred.

    Step 5.

    The intermediate deprotonates Glu201.

    Step 6.

    Inferred return step. Lys172 returns to its positive state via a water molecule.


    The products of the reaction.

Reaction Parameters

  • Kinetic Parameters
    Organism KM Value [mM] Substrate Comment
    Salmonella enterica subsp. enterica serovar Typhimurium 0.00004 5-phospho-alpha-D-ribose 1-diphosphate mutant E214A
  • Temperature

    There are no reaction parameters information for this Enzyme.

  • pH
    Organism pH Range Comment
    Sus scrofa 5.2 - 7.8 half maximal activity at pH 5.2 and pH 7.8
    Mycobacterium tuberculosis 5.2 - 11 activity cannot be detected at pH values below 5.2 and above 11.0
    Bos taurus 6.4 - 7.3 pH 6.4: about 50% of maximal activity, pH 7.3: about 55% of maximal activity

Associated Proteins

Protein name Organism
Nicotinate-nucleotide pyrophosphorylase [carboxylating] Human
Probable nicotinate-nucleotide pyrophosphorylase [carboxylating] Helicobacter pylori (strain ATCC 700392 / 26695)
Nicotinate-nucleotide pyrophosphorylase [carboxylating], chloroplastic Mouse-ear cress
Nicotinate-nucleotide pyrophosphorylase homolog,carboxylating Staphylococcus carnosus (strain TM300)
Nicotinate-nucleotide pyrophosphorylase (Carboxylating) protein Rhizobium etli (strain CIAT 652)