5TIW

Schistosoma haematobium (Blood Fluke) Sulfotransferase/Racemic Oxamniquine Complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.66 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 

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
Sulfotransferase
A, B
253Schistosoma haematobiumMutation(s): 0 
Gene Names: MS3_07706
UniProt
Find proteins for A0A094ZWQ2 (Schistosoma haematobium)
Explore A0A094ZWQ2 
Go to UniProtKB:  A0A094ZWQ2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A094ZWQ2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
A3P
Query on A3P

Download Ideal Coordinates CCD File 
C [auth A],
J [auth B]
ADENOSINE-3'-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
WHTCPDAXWFLDIH-KQYNXXCUSA-N
OAQ
Query on OAQ

Download Ideal Coordinates CCD File 
D [auth A],
K [auth B]
{(2S)-7-nitro-2-[(propan-2-ylamino)methyl]-1,2,3,4-tetrahydroquinolin-6-yl}methanol
C14 H21 N3 O3
XCGYUJZMCCFSRP-LBPRGKRZSA-N
BCN
Query on BCN

Download Ideal Coordinates CCD File 
H [auth A]BICINE
C6 H13 N O4
FSVCELGFZIQNCK-UHFFFAOYSA-N
PGE
Query on PGE

Download Ideal Coordinates CCD File 
M [auth B]TRIETHYLENE GLYCOL
C6 H14 O4
ZIBGPFATKBEMQZ-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A],
I [auth A],
L [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.66 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.67α = 90
b = 139.416β = 90
c = 49.56γ = 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, Derived calculations, Refinement description