PDBsum entry 1qpq

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Transferase PDB id
Protein chains
(+ 0 more) 284 a.a. *
SO4 ×6
NTM ×6
Waters ×266
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of quinolinic acid phosphoribosyltransferase from mycobacterium tuberculosis: a potential tb drug target
Structure: Quinolinate phosphoribosyltransferase. Chain: a, b, c, d, e, f. Synonym: nicotinate-nucleotide pyrophosphorylase, qaprtase. Engineered: yes
Source: Mycobacterium tuberculosis h37rv. Organism_taxid: 83332. Strain: h37rv. Gene: nadc. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.45Å     R-factor:   0.178     R-free:   0.253
Authors: V.Sharma,C.Grubmeyer,J.C.Sacchettini,Tb Structural Genomics Consortium (Tbsgc)
Key ref:
V.Sharma et al. (1998). Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target. Structure, 6, 1587-1599. PubMed id: 9862811 DOI: 10.1016/S0969-2126(98)00156-7
20-Nov-98     Release date:   25-Nov-98    
Go to PROCHECK summary

Protein chains
P9WJJ7  (NADC_MYCTU) -  Nicotinate-nucleotide pyrophosphorylase [carboxylating]
285 a.a.
284 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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!
  Cellular component     cell wall   2 terms 
  Biological process     pyridine nucleotide biosynthetic process   2 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1016/S0969-2126(98)00156-7 Structure 6:1587-1599 (1998)
PubMed id: 9862811  
Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target.
V.Sharma, C.Grubmeyer, J.C.Sacchettini.
Background:. Mycobacterium tuberculosis is the single most deadly human pathogen and is responsible for nearly three million deaths every year. Recent elucidation of the mode of action of isoniazid, a frontline antimycobacterial drug, suggests that NAD metabolism is extremely critical for this microorganism. M. tuberculosis depends solely on the de novo pathway to meet its NAD demand. Quinolinic acid phosphoribosyltransferase (QAPRTase), a key enzyme in the de novo biosynthesis of NAD, provides an attractive target for designing novel antitubercular drugs. Results:. The X-ray crystal structure of the M. tuberculosis QAPRTase apoenzyme has been determined by multiple isomorphous replacement at 2.4 A resolution. Structures of the enzyme have also been solved in complex with the substrate quinolinic acid (QA), the inhibitory QA analog phthalic acid (PA), the product nicotinate mononucleotide (NAMN), and as a ternary complex with PA and a substrate analog, 5-phosphoribosyl-1-(beta-methylene)pyrophosphate (PRPCP). The structure of the nonproductive QAPRTase-PA-PRPCP Michaelis complex reveals a 5-phosphoribosyl-1-pyrophosphate-binding site that is different from the one observed in type I phosphoribosyltransferases (PRTases). The type II PRTase active site of QAPRTase undergoes conformational changes that appear to be important in determining substrate specificity and eliciting productive catalysis. Conclusions:. QAPRTase is the only known representative of the type II PRTase fold, an unusual alpha/beta barrel, and appears to represent convergent evolution for PRTase catalysis. The active site of type II PRTase bears little resemblance to the better known type I enzymes.
  Selected figure(s)  
Figure 5.
Figure 5. Substrate-induced conformational changes in QAPRTase. Stereoview ribbon representation of the ternary complex of the enzyme showing the location of two substrate analogs, PA and PRPCP, in the fold. The color scheme is the same as for one monomer in Figure 2a. The conformations of helices a6A and a2' in the apoenzyme are superimposed (shown in green). The orientation of the Lys172 sidechain in both of the conformers is shown. The sidechain amine of Lys172 interacts with the C2 carboxylate of PA (or QA) in the substrate-bound form and with Glu104' in the unliganded or NAMN-bound form. (The figure was created using the program SETOR [36].)
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1587-1599) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20179338 T.C.Terwilliger (2010).
Rapid model building of alpha-helices in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 268-275.  
20179339 T.C.Terwilliger (2010).
Rapid model building of beta-sheets in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 276-284.  
20179340 T.C.Terwilliger (2010).
Rapid chain tracing of polypeptide backbones in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 285-294.  
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.  
18490451 H.I.Boshoff, X.Xu, K.Tahlan, C.S.Dowd, K.Pethe, L.R.Camacho, T.H.Park, C.S.Yun, D.Schnappinger, S.Ehrt, K.J.Williams, and C.E.Barry (2008).
Biosynthesis and recycling of nicotinamide cofactors in mycobacterium tuberculosis. An essential role for NAD in nonreplicating bacilli.
  J Biol Chem, 283, 19329-19341.  
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
17514677 S.E.Lee, J.S.Seo, Y.S.Keum, K.J.Lee, and Q.X.Li (2007).
Fluoranthene metabolism and associated proteins in Mycobacterium sp. JS14.
  Proteomics, 7, 2059-2069.  
16826227 A.Mattevi (2006).
A close look at NAD biosynthesis.
  Nat Struct Mol Biol, 13, 563-564.  
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
17154531 K.S.Champagne, E.Piscitelli, and C.S.Francklyn (2006).
Substrate recognition by the hetero-octameric ATP phosphoribosyltransferase from Lactococcus lactis.
  Biochemistry, 45, 14933-14943.  
16391116 K.Wang, K.Conn, and G.Lazarovits (2006).
Involvement of quinolinate phosphoribosyl transferase in promotion of potato growth by a Burkholderia strain.
  Appl Environ Microbiol, 72, 760-768.  
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
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
12915092 M.Bellinzoni, and G.Riccardi (2003).
Techniques and applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.
  Trends Microbiol, 11, 351-358.  
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.  
11876660 H.Cao, B.L.Pietrak, and C.Grubmeyer (2002).
Quinolinate phosphoribosyltransferase: kinetic mechanism for a type II PRTase.
  Biochemistry, 41, 3520-3528.  
11773618 M.A.Schumacher, C.J.Bashor, M.H.Song, K.Otsu, S.Zhu, R.J.Parry, B.Ullman, and R.G.Brennan (2002).
The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase.
  Proc Natl Acad Sci U S A, 99, 78-83.
PDB codes: 1jlr 1jls
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
11114509 T.P.Begley, T.C.Appleby, and S.E.Ealick (2000).
The structural basis for the remarkable catalytic proficiency of orotidine 5'-monophosphate decarboxylase.
  Curr Opin Struct Biol, 10, 711-718.  
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.