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Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini
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. Triosepho...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180082/ https://www.ncbi.nlm.nih.gov/pubmed/30305716 http://dx.doi.org/10.1038/s41598-018-33479-8 |
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author | Son, Jonghyeon Kim, Sulhee Kim, So Eun Lee, Haemin Lee, Myoung-Ro Hwang, Kwang Yeon |
author_facet | Son, Jonghyeon Kim, Sulhee Kim, So Eun Lee, Haemin Lee, Myoung-Ro Hwang, Kwang Yeon |
author_sort | Son, Jonghyeon |
collection | PubMed |
description | 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 3(10)-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. |
format | Online Article Text |
id | pubmed-6180082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61800822018-10-15 Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini Son, Jonghyeon Kim, Sulhee Kim, So Eun Lee, Haemin Lee, Myoung-Ro Hwang, Kwang Yeon Sci Rep Article 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 3(10)-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. Nature Publishing Group UK 2018-10-10 /pmc/articles/PMC6180082/ /pubmed/30305716 http://dx.doi.org/10.1038/s41598-018-33479-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Son, Jonghyeon Kim, Sulhee Kim, So Eun Lee, Haemin Lee, Myoung-Ro Hwang, Kwang Yeon Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini |
title | Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini |
title_full | Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini |
title_fullStr | Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini |
title_full_unstemmed | Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini |
title_short | Structural Analysis of an Epitope Candidate of Triosephosphate Isomerase in Opisthorchis viverrini |
title_sort | structural analysis of an epitope candidate of triosephosphate isomerase in opisthorchis viverrini |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180082/ https://www.ncbi.nlm.nih.gov/pubmed/30305716 http://dx.doi.org/10.1038/s41598-018-33479-8 |
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