2BSX

Crystal structure of the Plasmodium falciparum purine nucleoside phosphorylase complexed with inosine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.342 
  • R-Value Work: 0.264 
  • R-Value Observed: 0.268 

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This is version 1.3 of the entry. See complete history


Literature

Structures of Plasmodium Falciparum Purine Nucleoside Phosphorylase Complexed with Sulfate and its Natural Substrate Inosine

Schnick, C.Robien, M.A.Brzozowski, A.M.Dodson, E.J.Murshudov, G.N.Anderson, L.Luft, J.R.Mehlin, C.Hol, W.G.J.Brannigan, J.A.Wilkinson, A.J.

(2005) Acta Crystallogr D Biol Crystallogr 61: 1245

  • DOI: https://doi.org/10.1107/S0907444905020251
  • Primary Citation of Related Structures:  
    1SQ6, 2BSX

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5YW, England.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PURINE NUCLEOSIDE PHOSPHORYLASE253Plasmodium falciparum 3D7Mutation(s): 0 
EC: 2.4.2.1
UniProt
Find proteins for Q8I3X4 (Plasmodium falciparum (isolate 3D7))
Explore Q8I3X4 
Go to UniProtKB:  Q8I3X4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8I3X4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NOS
Query on NOS

Download Ideal Coordinates CCD File 
B [auth A]INOSINE
C10 H12 N4 O5
UGQMRVRMYYASKQ-KQYNXXCUSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.342 
  • R-Value Work: 0.264 
  • R-Value Observed: 0.268 
  • Space Group: P 3 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.117α = 90
b = 95.117β = 90
c = 47.075γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-08-18
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description