5TIZ

Schistosoma japonicum (Blood Fluke) Sulfotransferase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.87 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.230 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural and enzymatic insights into species-specific resistance to schistosome parasite drug therapy.

Taylor, A.B.Roberts, K.M.Cao, X.Clark, N.E.Holloway, S.P.Donati, E.Polcaro, C.M.Pica-Mattoccia, L.Tarpley, R.S.McHardy, S.F.Cioli, D.LoVerde, P.T.Fitzpatrick, P.F.Hart, P.J.

(2017) J Biol Chem 292: 11154-11164

  • DOI: https://doi.org/10.1074/jbc.M116.766527
  • Primary Citation of Related Structures:  
    5TIV, 5TIW, 5TIX, 5TIY, 5TIZ

  • PubMed Abstract: 

    The antischistosomal prodrug oxamniquine is activated by a sulfotransferase (SULT) in the parasitic flatworm Schistosoma mansoni. Of the three main human schistosome species, only S. mansoni is sensitive to oxamniquine therapy despite the presence of SULT orthologs in Schistosoma hematobium and Schistosoma japonicum The reason for this species-specific drug action has remained a mystery for decades. Here we present the crystal structures of S. hematobium and S. japonicum SULTs, including S. hematobium SULT in complex with oxamniquine. We also examined the activity of the three enzymes in vitro ; surprisingly, all three are active toward oxamniquine, yet we observed differences in catalytic efficiency that implicate kinetics as the determinant for species-specific toxicity. These results provide guidance for designing oxamniquine derivatives to treat infection caused by all species of schistosome to combat emerging resistance to current therapy.


  • Organizational Affiliation

    From the Departments of Biochemistry and Structural Biology and [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Sulfotransferase263Schistosoma japonicumMutation(s): 0 
UniProt
Find proteins for C1LER5 (Schistosoma japonicum)
Explore C1LER5 
Go to UniProtKB:  C1LER5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupC1LER5
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
A3P
Query on A3P

Download Ideal Coordinates CCD File 
B [auth A]ADENOSINE-3'-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
WHTCPDAXWFLDIH-KQYNXXCUSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.87 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.230 
  • Space Group: P 41 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.308α = 90
b = 57.308β = 90
c = 181.47γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-05-31
    Type: Initial release
  • Version 1.1: 2017-06-07
    Changes: Database references
  • Version 1.2: 2017-07-19
    Changes: Database references
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description