6ooi

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

Structural highlights

6ooi is a 8 chain structure with sequence from Schistosoma mansoni. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.14Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TPIS_SCHMA Antigen to the host M.1 monoclonal antibody.

Publication Abstract from PubMed

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 (beta-alpha)8 barrel in which the dimer interface consists of alpha-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 alpha5 and beta6 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.

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 LD, Leyva-Navarro L, Brieba LG PLoS Negl Trop Dis. 2020 Jan 10;14(1):e0007815. doi:, 10.1371/journal.pntd.0007815. PMID:31923219^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jimenez-Sandoval P, Castro-Torres E, Gonzalez-Gonzalez R, Diaz-Quezada C, Gurrola M, Camacho-Manriquez LD, Leyva-Navarro L, Brieba LG. Crystal structures of Triosephosphate Isomerases from Taenia solium and Schistosoma mansoni provide insights for vaccine rationale and drug design against helminth parasites. PLoS Negl Trop Dis. 2020 Jan 10;14(1):e0007815. doi:, 10.1371/journal.pntd.0007815. PMID:31923219 doi:http://dx.doi.org/10.1371/journal.pntd.0007815