6OOI

Crystal structure of triosephosphate isomerase from Schistosoma mansoni in complex with 2PG


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.14 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.180 

wwPDB Validation 3D Report Full Report


This is version 1.1 of the entry. See complete history

Literature

Crystal structures of Triosephosphate Isomerases from Taenia solium and Schistosoma mansoni provide insights for vaccine rationale and drug design against helminth parasites.

Jimenez-Sandoval, P.Castro-Torres, E.Gonzalez-Gonzalez, R.Diaz-Quezada, C.Gurrola, M.Camacho-Manriquez, L.D.Leyva-Navarro, L.Brieba, L.G.

(2020) Plos Negl Trop Dis 14: e0007815-e0007815

  • DOI: 10.1371/journal.pntd.0007815
  • Primary Citation of Related Structures:  

  • PubMed Abstract: 
  • Triosephosphate isomerases (TPIs) from Taenia solium (TsTPI) and Schistosoma mansoni (SmTPI) are potential vaccine and drug targets against cysticercosis and schistosomiasis, respectively. This is due to the dependence of parasitic helminths on glyco ...

    Triosephosphate isomerases (TPIs) from Taenia solium (TsTPI) and Schistosoma mansoni (SmTPI) are potential vaccine and drug targets against cysticercosis and schistosomiasis, respectively. This is due to the dependence of parasitic helminths on glycolysis and because those proteins elicit an immune response, presumably due to their surface localization. Here we report the crystal structures of TsTPI and SmTPI in complex with 2-phosphoglyceric acid (2-PGA). Both TPIs fold into a dimeric (β-α)8 barrel in which the dimer interface consists of α-helices 2, 3, and 4, and swapping of loop 3. TPIs from parasitic helminths harbor a region of three amino acids knows as the SXD/E insert (S155 to E157 and S157 to D159 in TsTPI and SmTPI, respectively). This insert is located between α5 and β6 and is proposed to be the main TPI epitope. This region is part of a solvent-exposed 310-helix that folds into a hook-like structure. The crystal structures of TsTPI and SmTPI predicted conformational epitopes that could be used for vaccine design. Surprisingly, the epitopes corresponding to the SXD/E inserts are not the ones with the greatest immunological potential. SmTPI, but not TsTPI, habors a sole solvent exposed cysteine (SmTPI-S230) and alterations in this residue decrease catalysis. The latter suggests that thiol-conjugating agents could be used to target SmTPI. In sum, the crystal structures of SmTPI and TsTPI are a blueprint for targeted schistosomiasis and cysticercosis drug and vaccine development.


    Organizational Affiliation

    Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, México.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Triosephosphate isomerase
A, B, C, D, E, F, G, H
256Schistosoma mansoniMutation(s): 0 
Gene Names: TPI
EC: 5.3.1.1
Find proteins for P48501 (Schistosoma mansoni)
Go to UniProtKB:  P48501
Small Molecules
Ligands 4 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
NA
Query on NA

Download SDF File 
Download CCD File 
A, B, C, E, H
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
 Ligand Interaction
CL
Query on CL

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Download CCD File 
A, B, C, D, F, G
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
 Ligand Interaction
GOL
Query on GOL

Download SDF File 
Download CCD File 
C, H
GLYCEROL
GLYCERIN; PROPANE-1,2,3-TRIOL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
 Ligand Interaction
PGA
Query on PGA

Download SDF File 
Download CCD File 
A, B, C, D, E, F, G, H
2-PHOSPHOGLYCOLIC ACID
C2 H5 O6 P
ASCFNMCAHFUBCO-UHFFFAOYSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.14 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.180 
  • Space Group: P 43
Unit Cell:
Length (Å)Angle (°)
a = 108.050α = 90.00
b = 108.050β = 90.00
c = 182.720γ = 90.00
Software Package:
Software NamePurpose
Cootmodel building
Aimlessdata reduction
PHENIXrefinement
CrystalCleardata collection

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Consejo Nacional de Ciencia y Tecnologia (CONACYT)MexicoFronteras de la Ciencia 13

Revision History 

  • Version 1.0: 2020-01-08
    Type: Initial release
  • Version 1.1: 2020-01-22
    Type: Database references