5CXQ

Crystal Structure of Isoform 2 of Purine Nucleoside Phosphorylase from Schistosoma mansoni in APO form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 

Starting Model: experimental
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This is version 1.4 of the entry. See complete history


Literature

The molecular structure of Schistosoma mansoni PNP isoform 2 provides insights into the nucleoside selectivity of PNPs.

Torini, J.R.Romanello, L.Batista, F.A.H.Serrao, V.H.B.Faheem, M.Zeraik, A.E.Bird, L.Nettleship, J.Reddivari, Y.Owens, R.DeMarco, R.Borges, J.C.Brandao-Neto, J.Pereira, H.D.

(2018) PLoS One 13: e0203532-e0203532

  • DOI: https://doi.org/10.1371/journal.pone.0203532
  • Primary Citation of Related Structures:  
    5CXQ, 5CXS, 5KO5, 5KO6, 5TBS, 5TBT, 5TBU

  • PubMed Abstract: 

    Purine nucleoside phosphorylases (PNPs) play an important role in the blood fluke parasite Schistosoma mansoni as a key enzyme of the purine salvage pathway. Here we present the structural and kinetic characterization of a new PNP isoform from S. mansoni, SmPNP2. Thermofluorescence screening of different ligands suggested cytidine and cytosine are potential ligands. The binding of cytosine and cytidine were confirmed by isothermal titration calorimetry, with a KD of 27 μM for cytosine, and a KM of 76.3 μM for cytidine. SmPNP2 also displays catalytic activity against inosine and adenosine, making it the first described PNP with robust catalytic activity towards both pyrimidines and purines. Crystal structures of SmPNP2 with different ligands were obtained and comparison of these structures with the previously described S. mansoni PNP (SmPNP1) provided clues for the unique capacity of SmPNP2 to bind pyrimidines. When compared with the structure of SmPNP1, substitutions in the vicinity of SmPNP2 active site alter the architecture of the nucleoside base binding site thus permitting an alternative binding mode for nucleosides, with a 180° rotation from the canonical binding mode. The remarkable plasticity of this binding site enhances our understanding of the correlation between structure and nucleotide selectivity, thus suggesting new ways to analyse PNP activity.


  • Organizational Affiliation

    Laboratório de Biologia Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, São Paulo, Brazil.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Purine nucleoside phosphorylase288Schistosoma mansoniMutation(s): 0 
Gene Names: Smp_179110
EC: 2.4.2.1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 
  • Space Group: P 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.55α = 90
b = 99.55β = 90
c = 99.55γ = 90
Software Package:
Software NamePurpose
xia2data scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
xia2data reduction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Sao Paulo Research Foundation (FAPESP)Brazil2012/14223-9

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-03
    Type: Initial release
  • Version 1.1: 2018-09-26
    Changes: Data collection, Database references, Derived calculations
  • Version 1.2: 2019-04-17
    Changes: Author supporting evidence, Data collection
  • Version 1.3: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.4: 2023-09-27
    Changes: Data collection, Database references, Refinement description