Nicotinate-nucleotide pyrophosphorylase (carboxylating) (type II)

 

This is a type II Quinolinic acid phosphoribosyltransferase (QAPRTase).

This protein is required for the de novo biosynthesis of NAD in both prokaryotes and eukaryotes. 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 nine other enzymes, (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. Type II enzymes lack the type I PRPP-binding motif and have TIM barrel-like structure [PMID:9016724].

 

Reference Protein and Structure

Sequence
P43619 UniProt (2.4.2.19) IPR004393 (Sequence Homologues) (PDB Homologues)
Biological species
Saccharomyces cerevisiae S288c (Baker's yeast) Uniprot
PDB
3c2e - Crystal structure at 1.9A of the apo quinolinate phosphoribosyl transferase (BNA6) from Saccharomyces cerevisiae (1.9 Å) PDBe PDBsum 3c2e
Catalytic CATH Domains
3.20.20.70 CATHdb (see all for 3c2e)
Click To Show Structure

Enzyme Reaction (EC:2.4.2.19)

5-O-phosphonato-alpha-D-ribofuranosyl diphosphate(5-)
CHEBI:58017ChEBI
+
quinolinate(2-)
CHEBI:29959ChEBI
+
hydron
CHEBI:15378ChEBI
→
nicotinate D-ribonucleotide(2-)
CHEBI:57502ChEBI
+
carbon dioxide
CHEBI:16526ChEBI
+
diphosphate(3-)
CHEBI:33019ChEBI
Alternative enzyme names: NAD pyrophosphorylase, QAPRTase, Nicotinate mononucleotide pyrophosphorylase (carboxylating), Quinolinate phosphoribosyltransferase (decarboxylating), Quinolinic acid phosphoribosyltransferase, Quinolinic phosphoribosyltransferase, Nicotinate-nucleotide pyrophosphorylase (carboxylating), Nicotinate-nucleotide:diphosphate phospho-alpha-D-ribosyltransferase (carboxylating),

Enzyme Mechanism

Introduction

Phosphoribosyl transfer has been proposed to proceed via a unimolecular nucleophilic substitution (SN1 reaction) involving an oxycarbonium-like intermediate. In the first step of the reaction the sugar ring eliminates the diphosphate group. In the second step, the carboxylic acid group forms carbon dioxide, which initiates the nucleophilic addition of the pyridine nitrogen to the oxycarbonium-like intermediate to form the final products.

Catalytic Residues Roles

UniProt PDB* (3c2e)
Lys144 Lys144(143)A Helps stabilise the reactive intermediates and transition states formed during the course of the reaction. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. di Luccio E et al. (2008), Biochemistry, 47, 4039-4050. Comprehensive X-ray Structural Studies of the Quinolinate Phosphoribosyl Transferase (BNA6) fromSaccharomyces cerevisiae‡. DOI:10.1021/bi7020475. PMID:18321072.
  2. Eads JC et al. (1997), Structure, 5, 47-58. A new function for a common fold: the crystal structure of quinolinic acid phosphoribosyltransferase. DOI:10.1016/s0969-2126(97)00165-2. PMID:9016724.

Step 1.

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Catalytic Residues Roles

Residue Roles
Lys144(143)A electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Gemma L. Holliday