PDBsum entry 1upu

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protein ligands Protein-protein interface(s) links
Transferase PDB id
Protein chains
224 a.a. *
PO4 ×4
U5P ×4
Waters ×400
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of the uracil phosphoribosyltransferase, mutant c128v, bound to product uridine-1-monophosphate (ump)
Structure: Uracil phosphoribosyltransferase. Chain: d, c, b, a. Synonym: uprtase. Engineered: yes. Mutation: yes
Source: Toxoplasma gondii. Organism_taxid: 5811. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Homo-Dimer (from PDB file)
2.50Å     R-factor:   0.148    
Authors: M.A.Schumacher,D.Carter,D.Scott,D.Roos,B.Ullman,R.G.Brennan
Key ref:
M.A.Schumacher et al. (1998). Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding. EMBO J, 17, 3219-3232. PubMed id: 9628859 DOI: 10.1093/emboj/17.12.3219
16-Apr-98     Release date:   11-May-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q26998  (UPP_TOXGO) -  Uracil phosphoribosyltransferase
244 a.a.
224 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Uracil phosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: UMP + diphosphate = uracil + 5-phospho-alpha-D-ribose 1-diphosphate
Bound ligand (Het Group name = U5P)
corresponds exactly
Bound ligand (Het Group name = PO4)
matches with 55.00% similarity
= uracil
+ 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     metabolic process   2 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1093/emboj/17.12.3219 EMBO J 17:3219-3232 (1998)
PubMed id: 9628859  
Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.
M.A.Schumacher, D.Carter, D.M.Scott, D.S.Roos, B.Ullman, R.G.Brennan.
Uracil phosphoribosyltransferase (UPRTase) catalyzes the transfer of a ribosyl phosphate group from alpha-D-5-phosphoribosyl-1-pyrophosphate to the N1 nitrogen of uracil. The UPRTase from the opportunistic pathogen Toxoplasma gondii is a rational target for antiparasitic drug design. To aid in structure-based drug design studies against toxoplasmosis, the crystal structures of the T.gondii apo UPRTase (1.93 A resolution), the UPRTase bound to its substrate, uracil (2.2 A resolution), its product, UMP (2.5 A resolution), and the prodrug, 5-fluorouracil (2.3 A resolution), have been determined. These structures reveal that UPRTase recognizes uracil through polypeptide backbone hydrogen bonds to the uracil exocyclic O2 and endocyclic N3 atoms and a backbone-water-exocyclic O4 oxygen hydrogen bond. This stereochemical arrangement and the architecture of the uracil-binding pocket reveal why cytosine and pyrimidines with exocyclic substituents at ring position 5 larger than fluorine, including thymine, cannot bind to the enzyme. Strikingly, the T. gondii UPRTase contains a 22 residue insertion within the conserved PRTase fold that forms an extended antiparallel beta-arm. Leu92, at the tip of this arm, functions to cap the active site of its dimer mate, thereby inhibiting the escape of the substrate-binding water molecule.
  Selected figure(s)  
Figure 3.
Figure 3 Dimerization interface involving the -arm. Shown are the contacts made by the -arm (colored yellow) from one subunit to its dimer pair (colored blue). Only part of the -arm is shown for clarity. Labeled are those residues making dimer contacts, and these include Phe83 and Phe101, which stack against the N-terminus of A2', Tyr96 which is sandwiched between Arg46' and Arg53', and Thr90 which makes hydrogen bonds to the carbonyls of Pro231' and Gly232'. Also shown is Leu92, which encloses the active site of the other monomer. Enzyme-bound uracil and phosphate are displayed and colored by atom type, whereby red is oxygen, blue is nitrogen, gray is carbon, and magenta is phosphorous.
Figure 5.
Figure 5 Stereo view of the superimposition of UMP-bound UPRTase (red) and 5-fluorouracil-bound UPRTase (green) onto the uracil-bound UPRTase (blue). Note the rotation of the 5-fluorouracil ring that occurs to prevent steric clash between the fluorine atom and the C[ ]atom of Ala168. Also, the slightly 'pulled out' position of the uracil ring of the UMP moiety, compared with uracil, is revealed. Labeled are residues Ala168, Tyr228, which stacks over the uracil ring, and Asp235 which hydrogen bonds with the Tyr228. Wat1 of each complex is shown as an appropriately colored sphere. The double-headed arrow highlights the proximity of the fluorine atom of 5-fluorouracil to the C[ ]atom of Ala168. This figure was generated using O (Jones et al., 1991).
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1998, 17, 3219-3232) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17266529 J.E.Hyde (2007).
Targeting purine and pyrimidine metabolism in human apicomplexan parasites.
  Curr Drug Targets, 8, 31-47.  
16788187 F.Arsène-Ploetze, H.Nicoloff, B.Kammerer, J.Martinussen, and F.Bringel (2006).
Uracil salvage pathway in Lactobacillus plantarum: Transcription and genetic studies.
  J Bacteriol, 188, 4777-4786.  
15805589 K.A.Kantardjieff, C.Vasquez, P.Castro, N.M.Warfel, B.S.Rho, T.Lekin, C.Y.Kim, B.W.Segelke, T.C.Terwilliger, and B.Rupp (2005).
Structure of pyrR (Rv1379) from Mycobacterium tuberculosis: a persistence gene and protein drug target.
  Acta Crystallogr D Biol Crystallogr, 61, 355-364.
PDB code: 1w30
15752360 K.F.Jensen, S.Arent, S.Larsen, and L.Schack (2005).
Allosteric properties of the GTP activated and CTP inhibited uracil phosphoribosyltransferase from the thermoacidophilic archaeon Sulfolobus solfataricus.
  FEBS J, 272, 1440-1453.  
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
15155225 A.R.Dodgson, K.J.Dodgson, C.Pujol, M.A.Pfaller, and D.R.Soll (2004).
Clade-specific flucytosine resistance is due to a single nucleotide change in the FUR1 gene of Candida albicans.
  Antimicrob Agents Chemother, 48, 2223-2227.  
15140885 K.Chaudhary, J.A.Darling, L.M.Fohl, W.J.Sullivan, R.G.Donald, E.R.Pfefferkorn, B.Ullman, and D.S.Roos (2004).
Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii.
  J Biol Chem, 279, 31221-31227.  
15504867 W.W.Hope, L.Tabernero, D.W.Denning, and M.J.Anderson (2004).
Molecular mechanisms of primary resistance to flucytosine in Candida albicans.
  Antimicrob Agents Chemother, 48, 4377-4386.  
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
11900545 C.Bashor, J.M.Denu, R.G.Brennan, and B.Ullman (2002).
Kinetic mechanism of adenine phosphoribosyltransferase from Leishmania donovani.
  Biochemistry, 41, 4020-4031.  
12199906 E.Kashuba, V.Kashuba, T.Sandalova, G.Klein, and L.Szekely (2002).
Epstein-Barr virus encoded nuclear protein EBNA-3 binds a novel human uridine kinase/uracil phosphoribosyltransferase.
  BMC Cell Biol, 3, 23.  
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
11512524 D.C.McFadden, M.Camps, and J.C.Boothroyd (2001).
Resistance as a tool in the study of old and new drug targets in Toxoplasma.
  Drug Resist Updat, 4, 79-84.  
11726695 E.R.Bonner, J.N.D'Elia, B.K.Billips, and R.L.Switzer (2001).
Molecular recognition of pyr mRNA by the Bacillus subtilis attenuation regulatory protein PyrR.
  Nucleic Acids Res, 29, 4851-4865.  
10393170 C.L.Phillips, B.Ullman, R.G.Brennan, and C.P.Hill (1999).
Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani.
  EMBO J, 18, 3533-3545.
PDB codes: 1qb7 1qb8 1qcc 1qcd
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.  
9914248 J.L.Smith (1998).
Glutamine PRPP amidotransferase: snapshots of an enzyme in action.
  Curr Opin Struct Biol, 8, 686-694.  
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
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.