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Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1
Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransfer...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146385/ https://www.ncbi.nlm.nih.gov/pubmed/30245965 http://dx.doi.org/10.1016/j.apsb.2018.07.007 |
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author | Tian, Xiangge Wang, Chao Dong, Peipei An, Yue Zhao, Xinyu Jiang, Weiru Wang, Gang Hou, Jie Feng, Lei Wang, Yan Ge, Guangbo Huo, Xiaokui Ning, Jing Ma, Xiaochi |
author_facet | Tian, Xiangge Wang, Chao Dong, Peipei An, Yue Zhao, Xinyu Jiang, Weiru Wang, Gang Hou, Jie Feng, Lei Wang, Yan Ge, Guangbo Huo, Xiaokui Ning, Jing Ma, Xiaochi |
author_sort | Tian, Xiangge |
collection | PubMed |
description | Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin (AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate. The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by in vitro reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals. |
format | Online Article Text |
id | pubmed-6146385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-61463852018-09-21 Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1 Tian, Xiangge Wang, Chao Dong, Peipei An, Yue Zhao, Xinyu Jiang, Weiru Wang, Gang Hou, Jie Feng, Lei Wang, Yan Ge, Guangbo Huo, Xiaokui Ning, Jing Ma, Xiaochi Acta Pharm Sin B Original article Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin (AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate. The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by in vitro reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals. Elsevier 2018-09 2018-07-20 /pmc/articles/PMC6146385/ /pubmed/30245965 http://dx.doi.org/10.1016/j.apsb.2018.07.007 Text en © 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Tian, Xiangge Wang, Chao Dong, Peipei An, Yue Zhao, Xinyu Jiang, Weiru Wang, Gang Hou, Jie Feng, Lei Wang, Yan Ge, Guangbo Huo, Xiaokui Ning, Jing Ma, Xiaochi Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1 |
title | Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1 |
title_full | Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1 |
title_fullStr | Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1 |
title_full_unstemmed | Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1 |
title_short | Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1 |
title_sort | arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2a1 |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146385/ https://www.ncbi.nlm.nih.gov/pubmed/30245965 http://dx.doi.org/10.1016/j.apsb.2018.07.007 |
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