Opisthorchis viverrini, a parasitic trematode, was recategorized as a group 1 biological carcinogen because it causes opisthorchiasis, which may result in cholangiocarcinoma. A new strategy for controlling opisthorchiasis is needed because of issues such as drug resistance and reinfection. Triosephosphate isomerase (TIM), a key enzyme in energy metabolism, is regarded as a potential drug target and vaccine candidate against various pathogens. Here, we determined the crystal structures of wild-type and 3 variants of TIMs from O. viverrini (OvTIM) at high resolution. The unique tripeptide of parasite trematodes, the SAD motif, was located on the surface of OvTIM and contributed to forming a 310-helix of the following loop in a sequence-independent manner. Through thermal stability and structural analyses of OvTIM variants, we found that the SAD motif induced local structural alterations of the surface and was involved in the overall stability of OvTIM in a complementary manner with another parasite-specific residue, N115. Comparison of the surface characteristics between OvTIM and Homo sapiens TIM (HsTIM) and structure-based epitope prediction suggested that the SAD motif functions as an epitope.
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