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

Jonghyeon Son1, Sulhee Kim1, So Eun Kim1

  • 1Division of Biotechnology, College of Life Sciences & Biotechnology, Korea University, Seoul, 136-701, South Korea.

Scientific Reports
|October 12, 2018
PubMed

Insights

Opisthorchis viverrini triosephosphate isomerase (OvTIM) has a unique surface motif (SAD) that may serve as a drug target. This finding offers a new strategy for controlling opisthorchiasis, a disease linked to cancer.

Area of Science:

  • Parasitology
  • Structural Biology
  • Biochemistry

Background:

  • Opisthorchis viverrini is a biological carcinogen causing opisthorchiasis and cholangiocarcinoma.
  • Drug resistance and reinfection necessitate novel control strategies for opisthorchiasis.
  • Triosephosphate isomerase (TIM) is a crucial metabolic enzyme and a potential drug/vaccine target.

Purpose of the Study:

  • To determine the high-resolution crystal structures of wild-type and variant O. viverrini TIM (OvTIM).
  • To investigate the structural role and stability contributions of the unique surface SAD motif in OvTIM.
  • To explore the potential of the SAD motif as a target for therapeutic intervention.

Main Methods:

  • High-resolution X-ray crystallography of OvTIM wild-type and variants.
  • Thermal stability assays.
  • Structural analysis and comparison with Homo sapiens TIM (HsTIM).
  • Structure-based epitope prediction.

Main Results:

  • The crystal structures of OvTIM and three variants were determined.
  • A unique surface tripeptide motif (SAD) forms a 310-helix in a sequence-independent manner.
  • The SAD motif, along with residue N115, influences OvTIM's local surface structure and overall stability.
  • Structural comparison and epitope prediction suggest the SAD motif is a potential B-cell epitope.

Conclusions:

  • The SAD motif is a parasite-specific structural feature of OvTIM.
  • The SAD motif plays a role in OvTIM stability and surface structure.
  • OvTIM's SAD motif is a promising target for developing new anti-parasitic drugs or vaccines against opisthorchiasis.

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