PDBsum entry 1qap

Glycosyltransferase

PDB id: 1qap

Contents

Protein chains

289 a.a. *

Ligands

NTM ×2

Waters ×7

* Residue conservation analysis

PDB id:

1qap

Name:

Glycosyltransferase

Title:

Quinolinic acid phosphoribosyltransferase with bound quinolinic acid

Structure:

Quinolinic acid phosphoribosyltransferase. Chain: a, b. Synonym: quinolinate prtase, qaprtase, qaprt, qprt. Engineered: yes

Source:

Salmonella typhimurium. Organism_taxid: 602. Cell_line: bl21. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.80Å R-factor: 0.186 R-free: 0.274

Authors:

J.C.Eads,D.Ozturk,T.B.Wexler,C.Grubmeyer,J.C.Sacchettini

Key ref:

J.C.Eads et al. (1997). A new function for a common fold: the crystal structure of quinolinic acid phosphoribosyltransferase. Structure, 5, 47-58. PubMed id: 9016724 DOI: 10.1016/S0969-2126(97)00165-2

Date:

20-Sep-96 Release date: 12-Mar-97

Protein chains

P30012  (NADC_SALTY) -  Nicotinate-nucleotide pyrophosphorylase [carboxylating] from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)

Seq: 297 a.a.

Struc: 289 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.4.2.19 - nicotinate-nucleotide diphosphorylase (carboxylating).
• Reaction: nicotinate beta-D-ribonucleotide + CO2 + diphosphate = quinolinate + 5-phospho-alpha-D-ribose 1-diphosphate + 2 H⁺

nicotinate beta-D-ribonucleotide + CO2 + diphosphate = quinolinate + 5-phospho-alpha-D-ribose 1-diphosphate + 2 × H(+) (Bound ligand (Het Group name = NTM) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(97)00165-2

Structure 5:47-58 (1997)

PubMed id: 9016724

A new function for a common fold: the crystal structure of quinolinic acid phosphoribosyltransferase.

J.C.Eads, D.Ozturk, T.B.Wexler, C.Grubmeyer, J.C.Sacchettini.

ABSTRACT

BACKGROUND: Quinolinic acid (QA) is a neurotoxin and has been shown to be present at high levels in the central nervous system of patients with certain diseases, such as AIDS and meningitis. The enzyme quinolinic acid phosphoribosyltransferase (QAPRTase) provides the only route for QA metabolism and is also an essential step in de novo NAD biosynthesis. QAPRTase catalyzes the synthesis of nicotinic acid mononucleotide (NAMN) from QA and 5-phosphoribosyl-1-pyrophosphate (PRPP). The structures of several phosphoribosyltransferases (PRTases) have been reported, and all have shown a similar fold of a five-strandard beta sheet surrounded by four alpha helices. A conserved sequence motif of 13 residues is common to these 'type I' PRTases but is not observed in the QAPRTase sequence, suggestive of a different fold for this enzyme. RESULTS: The crystal structure of QAPRTase from Salmonella typhimurium has been determined with bound QA to 2.8 A resolution, and with bound NAMN to 3.0 A resolution. Most significantly, the enzyme shows a completely novel fold for a PRTase enzyme comprising a two-domain structure: a mixed alpha/beta N-terminal domain and an alpha/beta barrel-like domain containing seven beta strands. The active site is located at the C-terminal ends of the beta strands of the alpha/beta barrel, and is bordered by the N-terminal domain of the second subunit of the dimer. The active site is largely composed of a number of conserved charged residues that appear to be important for substrate binding and catalysis. CONCLUSIONS: The seven-stranded alpha/beta-barrel domain of QAPRTase is very similar in structure to the eight-stranded alpha/beta-barrel enzymes. The structure shows a phosphate-binding site that appears to be conserved among many alpha/beta-barrel enzymes including indole-3-glycerol phosphate synthase and flavocytochrome b2. The new fold observed here demonstrates that the PRTase enzymes have evolved their similar chemistry from at least two completely different protein architectures.

Selected figure(s)

Figure 9.
Figure 9. Overlay of the phosphate-binding site regions of QAPRTase (in blue), flavocytochrome b2 (in magenta) and indole-3-glycerol phosphate synthase (in green). The bound NAMN is shown in stick form with atom coloring as in Figure 6.

The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 47-58) copyright 1997.

Figure was selected by an automated process.