Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini

Jonghyeon Son, Sulhee Kim, So Eun Kim, Haemin Lee, Myoung Ro Lee, Kwang Yeon Hwang

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number15075
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (2017R1A2B2005666 and 2018M3A9F3055925). S.K. was supported by Wiset program. We thank the supporting staff of beamline BL5C and BL11C of the Pohang Accelerator Light Source (Pohang, South Korea) and beamline BL44XU of Spring-8 (Hyogo, Japan) for providing help with data collection. We also acknowledge the Korean Basic Science Institute (Daejeon, Korea) for the use of a circular dichroism spectrophotometer.

Publisher Copyright:
© 2018, The Author(s).

ASJC Scopus subject areas

  • General

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