3F8W

Crystal structure of Schistosoma mansoni purine nucleoside phosphorylase in complex with adenosine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 

Starting Model: experimental
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This is version 1.3 of the entry. See complete history


Literature

Adenosine binding to low-molecular-weight purine nucleoside phosphorylase: the structural basis for recognition based on its complex with the enzyme from Schistosoma mansoni.

Pereira, H.M.Rezende, M.M.Castilho, M.S.Oliva, G.Garratt, R.C.

(2010) Acta Crystallogr D Biol Crystallogr 66: 73-79

  • DOI: https://doi.org/10.1107/S0907444909045715
  • Primary Citation of Related Structures:  
    3E9R, 3F8W, 3FAZ, 3FNQ

  • PubMed Abstract: 

    Schistosomes are unable to synthesize purines de novo and depend exclusively on the salvage pathway for their purine requirements. It has been suggested that blockage of this pathway could lead to parasite death. The enzyme purine nucleoside phosphorylase (PNP) is one of its key components and molecules designed to inhibit the low-molecular-weight (LMW) PNPs, which include both the human and schistosome enzymes, are typically analogues of the natural substrates inosine and guanosine. Here, it is shown that adenosine both binds to Schistosoma mansoni PNP and behaves as a weak micromolar inhibitor of inosine phosphorolysis. Furthermore, the first crystal structures of complexes of an LMW PNP with adenosine and adenine are reported, together with those with inosine and hypoxanthine. These are used to propose a structural explanation for the selective binding of adenosine to some LMW PNPs but not to others. The results indicate that transition-state analogues based on adenosine or other 6-amino nucleosides should not be discounted as potential starting points for alternative inhibitors.


  • Organizational Affiliation

    Instituto de Física de São Carlos, Universidade de São Paulo, Avenida Trabalhador Sãocarlense 400, São Carlos, SP 13560-970, Brazil. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Purine-nucleoside phosphorylase
A, B, C
287Schistosoma mansoniMutation(s): 0 
Gene Names: SmPNP
EC: 2.4.2.1
UniProt
Find proteins for Q9BMI9 (Schistosoma mansoni)
Explore Q9BMI9 
Go to UniProtKB:  Q9BMI9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BMI9
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ADN
Query on ADN

Download Ideal Coordinates CCD File 
D [auth A],
H [auth B],
J [auth C]
ADENOSINE
C10 H13 N5 O4
OIRDTQYFTABQOQ-KQYNXXCUSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B],
K [auth C]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
DMS
Query on DMS

Download Ideal Coordinates CCD File 
F [auth A],
G [auth B],
L [auth C]
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ADN PDBBind:  3F8W IC50: 8.23e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.715α = 90
b = 121.273β = 90
c = 133.248γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
MOLREPphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
MAR345data collection
DENZOdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-11-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description