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Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway
Glutathione (GSH) conjugation was an important pathway to regulate the toxicity of microcystins (MCs) targeted to protein phosphatases. To explore the specific molecular mechanism for GSH detoxification, two typical MC-GSHs (derived from MCLR and MCRR) were synthesized, prepared, and purified accord...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350311/ https://www.ncbi.nlm.nih.gov/pubmed/28337461 http://dx.doi.org/10.1155/2017/9676504 |
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author | Zong, Wansong Wang, Xiaoning Du, Yonggang Zhang, Shuhan Zhang, Ying Teng, Yue |
author_facet | Zong, Wansong Wang, Xiaoning Du, Yonggang Zhang, Shuhan Zhang, Ying Teng, Yue |
author_sort | Zong, Wansong |
collection | PubMed |
description | Glutathione (GSH) conjugation was an important pathway to regulate the toxicity of microcystins (MCs) targeted to protein phosphatases. To explore the specific molecular mechanism for GSH detoxification, two typical MC-GSHs (derived from MCLR and MCRR) were synthesized, prepared, and purified according to previous research. Then, the reduced inhibition effect for MC-GSHs on protein phosphatase 1 was verified by comparing with their original toxins. To further clarify the molecular mechanism for MC-GSHs detoxification, we evaluated the interactions between MCs/MC-GSHs and PP1 with the assistance of MOE molecule simulation. When GSH was introduced to MCs, the covalent binding (Mdha(7) to Cys(273)), the hydrophobic interaction (Adda(5) with PP1), the hydrogen bonds (especially for Lys(2)-Arg(96) and Glu(6)-Tyr(272)), the covalent combination (between Mdha(7) and Cys(273)), and the ion bonds (between Mn(2+) and Asn(124)/His(248)/Asp(64)/His(66)) of MCLR/MCRR-PP1 complexes weakened to a certain extent, while the ion bonds between Mn(2+) and His(173)/Asp(92) residues increased. It was not difficult to find that the toxicity of MCs was closely related to the above sites/interactions and the above key information for MCs-PP1; MC-GSHs-PP1 complexes were important for clarifying the detoxification mechanism of MC-GSHs pathway. This study offers a comprehensive cognition on MCs toxicity regulation and provides valid theoretical support to control their potential risk. |
format | Online Article Text |
id | pubmed-5350311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-53503112017-03-23 Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway Zong, Wansong Wang, Xiaoning Du, Yonggang Zhang, Shuhan Zhang, Ying Teng, Yue Biomed Res Int Research Article Glutathione (GSH) conjugation was an important pathway to regulate the toxicity of microcystins (MCs) targeted to protein phosphatases. To explore the specific molecular mechanism for GSH detoxification, two typical MC-GSHs (derived from MCLR and MCRR) were synthesized, prepared, and purified according to previous research. Then, the reduced inhibition effect for MC-GSHs on protein phosphatase 1 was verified by comparing with their original toxins. To further clarify the molecular mechanism for MC-GSHs detoxification, we evaluated the interactions between MCs/MC-GSHs and PP1 with the assistance of MOE molecule simulation. When GSH was introduced to MCs, the covalent binding (Mdha(7) to Cys(273)), the hydrophobic interaction (Adda(5) with PP1), the hydrogen bonds (especially for Lys(2)-Arg(96) and Glu(6)-Tyr(272)), the covalent combination (between Mdha(7) and Cys(273)), and the ion bonds (between Mn(2+) and Asn(124)/His(248)/Asp(64)/His(66)) of MCLR/MCRR-PP1 complexes weakened to a certain extent, while the ion bonds between Mn(2+) and His(173)/Asp(92) residues increased. It was not difficult to find that the toxicity of MCs was closely related to the above sites/interactions and the above key information for MCs-PP1; MC-GSHs-PP1 complexes were important for clarifying the detoxification mechanism of MC-GSHs pathway. This study offers a comprehensive cognition on MCs toxicity regulation and provides valid theoretical support to control their potential risk. Hindawi Publishing Corporation 2017 2017-02-27 /pmc/articles/PMC5350311/ /pubmed/28337461 http://dx.doi.org/10.1155/2017/9676504 Text en Copyright © 2017 Wansong Zong et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zong, Wansong Wang, Xiaoning Du, Yonggang Zhang, Shuhan Zhang, Ying Teng, Yue Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway |
title | Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway |
title_full | Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway |
title_fullStr | Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway |
title_full_unstemmed | Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway |
title_short | Molecular Mechanism for the Regulation of Microcystin Toxicity to Protein Phosphatase 1 by Glutathione Conjugation Pathway |
title_sort | molecular mechanism for the regulation of microcystin toxicity to protein phosphatase 1 by glutathione conjugation pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350311/ https://www.ncbi.nlm.nih.gov/pubmed/28337461 http://dx.doi.org/10.1155/2017/9676504 |
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