Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanisms

nicotinate-nucleotide diphosphorylase (carboxylating) (type II) By Reference

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.




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Step 5
• Step 6
• Products

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.



Products.

The products of the reaction.

View All 2 Reaction Mechanisms in M-CSA

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

Citations

• Phyllosphere microbial community of cigar tobacco and its corresponding metabolites.
• Effect of Phosphoribosyltransferase Down-regulation on Malignant Glioma Cell Characteristics.
• Integrated Analysis of lncRNA and circRNA Mediated ceRNA Regulatory Networks in Skin Reveals Innate Immunity Differences Between Wild-Type and Yellow Mutant Rainbow Trout (Oncorhynchus mykiss).
• Identification of flux trade-offs in metabolic networks.
• Knockdown of Quinolinate Phosphoribosyltransferase Results in Decreased Salicylic Acid-Mediated Pathogen Resistance in Arabidopsis thaliana.
• Genetic evidence for Magnaporthe oryzae vitamin B3 acquisition from rice cells.
• Expression of a tobacco nicotine biosynthesis gene depends on the JRE4 transcription factor in heterogenous tomato.
• A network pharmacology-based approach to explore mechanism of action of medicinal herbs for alopecia treatment.
• Organ Co-Relationship in Tryptophan Metabolism and Factors That Govern the Biosynthesis of Nicotinamide from Tryptophan.
• Cloning and functional characterization of quinolinic acid phosphoribosyl transferase (QPT) gene of Nicotiana tabacum.
• The Ethanolic Extract of Lindera aggregata Modulates Gut Microbiota Dysbiosis and Alleviates Ethanol-Induced Acute Liver Inflammation and Oxidative Stress SIRT1/Nrf2/NF-κB Pathway.