spacer
spacer

PDBsum entry 1qap

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Glycosyltransferase PDB id
1qap
Jmol
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    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P30012  (NADC_SALTY) -  Nicotinate-nucleotide pyrophosphorylase [carboxylating]
Seq:
Struc:
297 a.a.
289 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* 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).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Beta-nicotinate D-ribonucleotide + diphosphate + CO2 = pyridine-2,3- dicarboxylate + 5-phospho-alpha-D-ribose 1-diphosphate
Beta-nicotinate D-ribonucleotide
+ diphosphate
+ CO(2)
=
pyridine-2,3- dicarboxylate
Bound ligand (Het Group name = NTM)
corresponds exactly
+ 5-phospho-alpha-D-ribose 1-diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     pyridine nucleotide biosynthetic process   2 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20047307 Z.Bello, B.Stitt, and C.Grubmeyer (2010).
Interactions at the 2 and 5 positions of 5-phosphoribosyl pyrophosphate are essential in Salmonella typhimurium quinolinate phosphoribosyltransferase.
  Biochemistry, 49, 1377-1387.  
20047306 Z.Bello, and C.Grubmeyer (2010).
Roles for cationic residues at the quinolinic acid binding site of quinolinate phosphoribosyltransferase.
  Biochemistry, 49, 1388-1395.  
17763926 M.K.Kim, G.B.Kang, W.K.Song, and S.H.Eom (2007).
The role of Phe181 in the hexamerization of Helicobacter pylori quinolinate phosphoribosyltransferase.
  Protein J, 26, 517-521.  
17894860 P.S.Monzani, S.Trapani, O.H.Thiemann, and G.Oliva (2007).
Crystal structure of Leishmania tarentolae hypoxanthine-guanine phosphoribosyltransferase.
  BMC Struct Biol, 7, 59.
PDB code: 1pzm
16783377 J.A.Khan, X.Tao, and L.Tong (2006).
Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents.
  Nat Struct Mol Biol, 13, 582-588.
PDB codes: 2gvg 2gvj 2gvl
16419067 M.K.Kim, Y.J.Im, J.H.Lee, and S.H.Eom (2006).
Crystal structure of quinolinic acid phosphoribosyltransferase from Helicobacter pylori.
  Proteins, 63, 252-255.
PDB codes: 2b7n 2b7p 2b7q
16714288 M.Marino, M.Deuss, D.I.Svergun, P.V.Konarev, R.Sterner, and O.Mayans (2006).
Structural and mutational analysis of substrate complexation by anthranilate phosphoribosyltransferase from Sulfolobus solfataricus.
  J Biol Chem, 281, 21410-21421.
PDB codes: 1zxy 1zyk 2gvq
16783373 T.Wang, X.Zhang, P.Bheda, J.R.Revollo, S.Imai, and C.Wolberger (2006).
Structure of Nampt/PBEF/visfatin, a mammalian NAD+ biosynthetic enzyme.
  Nat Struct Mol Biol, 13, 661-662.
PDB codes: 2h3b 2h3d
15753098 D.H.Shin, N.Oganesyan, J.Jancarik, H.Yokota, R.Kim, and S.H.Kim (2005).
Crystal structure of a nicotinate phosphoribosyltransferase from Thermoplasma acidophilum.
  J Biol Chem, 280, 18326-18335.
PDB codes: 1ytd 1yte 1ytk 2i1o
16154095 J.S.Chappie, J.M.Cànaves, G.W.Han, C.L.Rife, Q.Xu, and R.C.Stevens (2005).
The structure of a eukaryotic nicotinic acid phosphoribosyltransferase reveals structural heterogeneity among type II PRTases.
  Structure, 13, 1385-1396.
PDB code: 1vlp
16051603 K.S.Champagne, M.Sissler, Y.Larrabee, S.Doublié, and C.S.Francklyn (2005).
Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog.
  J Biol Chem, 280, 34096-34104.
PDB codes: 1z7m 1z7n
15660995 M.C.Vega, P.Zou, F.J.Fernandez, G.E.Murphy, R.Sterner, A.Popov, and M.Wilmanns (2005).
Regulation of the hetero-octameric ATP phosphoribosyl transferase complex from Thermotoga maritima by a tRNA synthetase-like subunit.
  Mol Microbiol, 55, 675-686.
PDB code: 1usy
15689504 M.Kukimoto-Niino, R.Shibata, K.Murayama, H.Hamana, M.Nishimoto, Y.Bessho, T.Terada, M.Shirouzu, S.Kuramitsu, and S.Yokoyama (2005).
Crystal structure of a predicted phosphoribosyltransferase (TT1426) from Thermus thermophilus HB8 at 2.01 A resolution.
  Protein Sci, 14, 823-827.
PDB code: 1wd5
15103640 R.Schwarzenbacher, L.Jaroszewski, F.von Delft, P.Abdubek, E.Ambing, T.Biorac, L.S.Brinen, J.M.Canaves, J.Cambell, H.J.Chiu, X.Dai, A.M.Deacon, M.DiDonato, M.A.Elsliger, S.Eshagi, R.Floyd, A.Godzik, C.Grittini, S.K.Grzechnik, E.Hampton, C.Karlak, H.E.Klock, E.Koesema, J.S.Kovarik, A.Kreusch, P.Kuhn, S.A.Lesley, I.Levin, D.McMullan, T.M.McPhillips, M.D.Miller, A.Morse, K.Moy, J.Ouyang, R.Page, K.Quijano, A.Robb, G.Spraggon, R.C.Stevens, H.van den Bedem, J.Velasquez, J.Vincent, X.Wang, B.West, G.Wolf, Q.Xu, K.O.Hodgson, J.Wooley, and I.A.Wilson (2004).
Crystal structure of a type II quinolic acid phosphoribosyltransferase (TM1645) from Thermotoga maritima at 2.50 A resolution.
  Proteins, 55, 768-771.
PDB code: 1o4u
14675542 C.V.Smith, and J.C.Sacchettini (2003).
Mycobacterium tuberculosis: a model system for structural genomics.
  Curr Opin Struct Biol, 13, 658-664.  
12482852 G.K.Grabner, and R.L.Switzer (2003).
Kinetic studies of the uracil phosphoribosyltransferase reaction catalyzed by the Bacillus subtilis pyrimidine attenuation regulatory protein PyrR.
  J Biol Chem, 278, 6921-6927.  
12832780 M.K.Kim, Y.S.Kim, S.H.Rho, Y.J.Im, J.H.Lee, G.B.Kang, and S.H.Eom (2003).
Crystallization and preliminary X-ray crystallographic analysis of quinolinate phosphoribosyltransferase of Helicobacter pylori.
  Acta Crystallogr D Biol Crystallogr, 59, 1265-1266.  
12037295 A.Kadziola, J.Neuhard, and S.Larsen (2002).
Structure of product-bound Bacillus caldolyticus uracil phosphoribosyltransferase confirms ordered sequential substrate binding.
  Acta Crystallogr D Biol Crystallogr, 58, 936-945.
PDB code: 1i5e
11284686 N.Munagala, V.J.Basus, and C.C.Wang (2001).
Role of the flexible loop of hypoxanthine-guanine-xanthine phosphoribosyltransferase from Tritrichomonas foetus in enzyme catalysis.
  Biochemistry, 40, 4303-4311.  
10986466 I.D'Angelo, N.Raffaelli, V.Dabusti, T.Lorenzi, G.Magni, and M.Rizzi (2000).
Structure of nicotinamide mononucleotide adenylyltransferase: a key enzyme in NAD(+) biosynthesis.
  Structure, 8, 993.
PDB code: 1f9a
11080624 Z.Marković-Housley, G.Miglierini, L.Soldatova, P.J.Rizkallah, U.Müller, and T.Schirmer (2000).
Crystal structure of hyaluronidase, a major allergen of bee venom.
  Structure, 8, 1025-1035.
PDB codes: 1fcq 1fcu 1fcv
10425677 A.Mattevi, G.Tedeschi, L.Bacchella, A.Coda, A.Negri, and S.Ronchi (1999).
Structure of L-aspartate oxidase: implications for the succinate dehydrogenase/fumarate reductase oxidoreductase family.
  Structure, 7, 745-756.
PDB code: 1chu
10079076 C.Lundegaard, and K.F.Jensen (1999).
Kinetic mechanism of uracil phosphoribosyltransferase from Escherichia coli and catalytic importance of the conserved proline in the PRPP binding site.
  Biochemistry, 38, 3327-3334.  
9890908 G.P.Wang, C.Lundegaard, K.F.Jensen, and C.Grubmeyer (1999).
Kinetic mechanism of OMP synthase: a slow physical step following group transfer limits catalytic rate.
  Biochemistry, 38, 275-283.  
10089375 L.Bacchella, C.Lina, F.Todone, A.Negri, G.Tedeschi, S.Ronchi, and A.Mattevi (1999).
Crystallization of L-aspartate oxidase, the first enzyme in the bacterial de novo biosynthesis of NAD.
  Acta Crystallogr D Biol Crystallogr, 55, 549-551.  
9521670 C.C.Lee, S.P.Craig, and A.E.Eakin (1998).
A single amino acid substitution in the human and a bacterial hypoxanthine phosphoribosyltransferase modulates specificity for the binding of guanine.
  Biochemistry, 37, 3491-3498.  
9551555 D.R.Tomchick, R.J.Turner, R.L.Switzer, and J.L.Smith (1998).
Adaptation of an enzyme to regulatory function: structure of Bacillus subtilis PyrR, a pyr RNA-binding attenuation protein and uracil phosphoribosyltransferase.
  Structure, 6, 337-350.
PDB codes: 1a3c 1a4x
9628859 M.A.Schumacher, D.Carter, D.M.Scott, D.S.Roos, B.Ullman, and R.G.Brennan (1998).
Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.
  EMBO J, 17, 3219-3232.
PDB codes: 1bd3 1bd4 1upf 1upu
9521740 M.Rajavel, D.Lalo, J.W.Gross, and C.Grubmeyer (1998).
Conversion of a cosubstrate to an inhibitor: phosphorylation mutants of nicotinic acid phosphoribosyltransferase.
  Biochemistry, 37, 4181-4188.  
9860824 P.J.Focia, S.P.Craig, and A.E.Eakin (1998).
Approaching the transition state in the crystal structure of a phosphoribosyltransferase.
  Biochemistry, 37, 17120-17127.
PDB code: 1tc2
9790669 P.J.Focia, S.P.Craig, R.Nieves-Alicea, R.J.Fletterick, and A.E.Eakin (1998).
A 1.4 A crystal structure for the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi.
  Biochemistry, 37, 15066-15075.
PDB code: 1tc1
9862811 V.Sharma, C.Grubmeyer, and J.C.Sacchettini (1998).
Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target.
  Structure, 6, 1587-1599.
PDB codes: 1qpn 1qpo 1qpq 1qpr
9333323 J.M.Krahn, J.H.Kim, M.R.Burns, R.J.Parry, H.Zalkin, and J.L.Smith (1997).
Coupled formation of an amidotransferase interdomain ammonia channel and a phosphoribosyltransferase active site.
  Biochemistry, 36, 11061-11068.
PDB codes: 1ecb 1ecc
9271502 S.Chen, D.R.Tomchick, D.Wolle, P.Hu, J.L.Smith, R.L.Switzer, and H.Zalkin (1997).
Mechanism of the synergistic end-product regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase by nucleotides.
  Biochemistry, 36, 10718-10726.
PDB code: 1ao0
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.