PDBsum entry 2bsx

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Transferase PDB id
Protein chain
241 a.a. *
Waters ×105
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of the plasmodium falciparum purine nucleoside phosphorylase complexed with inosine
Structure: Purine nucleoside phosphorylase. Chain: a. Engineered: yes
Source: Plasmodium falciparum. Organism_taxid: 36329. Strain: 3d7. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Hexamer (from PDB file)
2.0Å     R-factor:   0.268     R-free:   0.342
Authors: C.Schnick,A.M.Brzozowski,E.J.Dodson,G.N.Murshudov, J.A.Brannigan,A.J.Wilkinson
Key ref:
C.Schnick et al. (2005). Structures of Plasmodium falciparum purine nucleoside phosphorylase complexed with sulfate and its natural substrate inosine. Acta Crystallogr D Biol Crystallogr, 61, 1245-1254. PubMed id: 16131758 DOI: 10.1107/S0907444905020251
24-May-05     Release date:   18-Aug-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q8I3X4  (Q8I3X4_PLAF7) -  Purine nucleotide phosphorylase, putative
245 a.a.
241 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Uridine phosphorylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
Bound ligand (Het Group name = NOS)
matches with 71.00% similarity
+ phosphate
= uracil
+ alpha-D-ribose 1-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     nucleoside metabolic process   1 term 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1107/S0907444905020251 Acta Crystallogr D Biol Crystallogr 61:1245-1254 (2005)
PubMed id: 16131758  
Structures of Plasmodium falciparum purine nucleoside phosphorylase complexed with sulfate and its natural substrate inosine.
C.Schnick, M.A.Robien, A.M.Brzozowski, E.J.Dodson, G.N.Murshudov, L.Anderson, J.R.Luft, C.Mehlin, W.G.Hol, J.A.Brannigan, A.J.Wilkinson.
Purine metabolism in the parasite Plasmodium has been identified as a promising target for antimalarial therapies. Purine nucleoside phosphorylase (PNP) is part of a salvage pathway for the biosynthesis of purines, which are essential for parasite survival. Two crystal structures of PNP from Plasmodium falciparum (PfPNP) in two space groups, each with a single subunit in the asymmetric unit, are described here. One structure, refined to 2.4 A, has an empty nucleoside-binding site and a sulfate ion bound in the phosphate-binding pocket. The second structure, refined to 2.0 A, has the substrate inosine bound to the active centre. Structure comparison reveals alterations in the active site upon ligand binding. The new structures presented here specifically highlight the likely roles of Asp206 and two loops flanking the active site: the beta7-alpha6 loop (residues approximately 161-169) and the beta9-alpha8 loop (residues approximately 208-223). Comparison with PNP in complex with transition-state inhibitors suggests that the purine substrate moves towards the phosphate substrate, rather than vice versa, upon forming the transition state. The single-substrate-containing PfPNP structures also appear to be more flexible than PfPNP bound to inhibitors. Together, these structures serve as a basis for better understanding of ligand binding and mechanism that can be further exploited to optimize the specificity of anti-PfPNP drugs.
  Selected figure(s)  
Figure 1.
Figure 1 Phosphorolysis of inosine catalysed by P. falciparum PNP. The product hypoxanthine is the major precursor for the purine-salvage pathway.
Figure 2.
Figure 2 Overall structure of the PfPNP subunit. (a) Section of the stick model coloured by atom of PfPNP-ino with electron density displayed (omit map) at 0.5 . (b) Section of the model of PfPNP-ino with 2F[o] - F[c] electron density displayed at 1.0 . (c) Superposition of the PfPNP-ino structure (light green) and the PfPNP-SO[4] structure (blue). Inosine is shown in red and sulfate in yellow. This and subsequent figures were generated using PyMol (DeLano, 2002[DeLano, W. L. (2002). The PyMOL Molecular Graphics System. DeLano Scientific, San Carlos, CA, USA. .]).
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2005, 61, 1245-1254) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20070944 E.T.Larson, D.G.Mudeppa, J.R.Gillespie, N.Mueller, A.J.Napuli, J.A.Arif, J.Ross, T.L.Arakaki, A.Lauricella, G.Detitta, J.Luft, F.Zucker, C.L.Verlinde, E.Fan, W.C.Van Voorhis, F.S.Buckner, P.K.Rathod, W.G.Hol, and E.A.Merritt (2010).
The crystal structure and activity of a putative trypanosomal nucleoside phosphorylase reveal it to be a homodimeric uridine phosphorylase.
  J Mol Biol, 396, 1244-1259.
PDB code: 3bje
19669809 F.B.Zanchi, R.A.Caceres, R.G.Stabeli, and Azevedo (2010).
Molecular dynamics studies of a hexameric purine nucleoside phosphorylase.
  J Mol Model, 16, 543-550.  
20210752 M.L.Bellows, and C.A.Floudas (2010).
Computational methods for de novo protein design and its applications to the human immunodeficiency virus 1, purine nucleoside phosphorylase, ubiquitin specific protease 7, and histone demethylases.
  Curr Drug Targets, 11, 264-278.  
19575810 A.Chaikuad, and R.L.Brady (2009).
Conservation of structure and activity in Plasmodium purine nucleoside phosphorylases.
  BMC Struct Biol, 9, 42.
PDB codes: 3emv 3enz
17639373 A.Modrak-Wójcik, A.Kirilenko, D.Shugar, and B.Kierdaszuk (2008).
Role of ionization of the phosphate cosubstrate on phosphorolysis by purine nucleoside phosphorylase (PNP) of bacterial (E. coli) and mammalian (human) origin.
  Eur Biophys J, 37, 153-164.  
17266529 J.E.Hyde (2007).
Targeting purine and pyrimidine metabolism in human apicomplexan parasites.
  Curr Drug Targets, 8, 31-47.  
16844998 A.P.Rodrigues, B.J.Grant, and R.E.Hubbard (2006).
sgTarget: a target selection resource for structural genomics.
  Nucleic Acids Res, 34, W225-W230.  
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.