6OOI

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

6OOI の概要

• エントリーDOI: 10.2210/pdb6ooi/pdb
• 分子名称: Triosephosphate isomerase, 2-PHOSPHOGLYCOLIC ACID, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: isomerase
• 由来する生物種: Schistosoma mansoni (Blood fluke)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 229480.79

構造登録者

Jimenez-Sandoval, P.,Brieba, L. (登録日: 2019-04-23, 公開日: 2020-01-08, 最終更新日: 2023-10-11)

主引用文献

Jimenez-Sandoval, P.,Castro-Torres, E.,Gonzalez-Gonzalez, R.,Diaz-Quezada, C.,Gurrola, M.,Camacho-Manriquez, L.D.,Leyva-Navarro, L.,Brieba, L.G.
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, 14:e0007815-e0007815, 2020

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 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.

PubMed: 31923219
DOI: 10.1371/journal.pntd.0007815

実験手法

X-RAY DIFFRACTION (2.14 Å)