The Importance of Val386 in Transmembrane Domain 8 for the Activation of OATP1B3 by Epigallocatechin Gallate
| العنوان: | The Importance of Val386 in Transmembrane Domain 8 for the Activation of OATP1B3 by Epigallocatechin Gallate |
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| المؤلفون: | Zhongmin Wang, Ying Li, Cecilia E. Villanueva, Taotao Peng, Wanjun Han, Zheyue Bo, Hongjian Zhang, Bruno Hagenbuch, Chunshan Gui |
| المصدر: | J Agric Food Chem |
| بيانات النشر: | American Chemical Society (ACS), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Kinetics, Solute Carrier Organic Anion Transporter Family Member 1B3, Liver-Specific Organic Anion Transporter 1, Organic Anion Transporters, Biological Transport, General Chemistry, Organic Anion Transporters, Sodium-Independent, General Agricultural and Biological Sciences, Article, Catechin |
| الوصف: | Estrone-3-sulfate (E3S) uptake mediated by organic anion transporting polypeptide 1B3 (OATP1B3) can be activated by epigallocatechin gallate (EGCG). In this study, by using chimeric transporters and site-directed mutagenesis, we found that Val386 in transmembrane domain 8 (TM8) is essential for OATP1B3’s activation by EGCG. Kinetic studies showed that the loss of activation of 1B3-TM8 and 1B3-V386F in the presence of EGCG is due to their decreased substrate binding affinity and reduced maximal transport rate. The overall transport efficiency of OATP1B3, 1B3-TM8, and 1B3-V386F in the absence and presence of EGCG were 8.6 ± 0.7 vs 15.9 ± 1.4 (p < 0.05), 11.2 ± 2.1 vs 2.7 ± 0.3 (p < 0.05), and 10.2 ± 1.0 vs 2.5 ± 0.3 (p < 0.05), respectively. While 1B3-V386F cannot be activated by EGCG, its transport activity for EGCG is also diminished. OATP1B3’s activation by EGCG is substrate-dependent as EGCG inhibits OATP1B3-mediated pravastatin uptake. Furthermore, the activation of OATP1B3-mediated E3S uptake by quercetin 3-O-α-L-arabinopyranosyl(1→2)-α-L-rhamnopyranoside is not affected by TM8 and V386F. Taken together, the activation of OATP1B3 by small molecules is substrate- and modulator-dependent and V386 in TM8 plays a critical role in the activation of OATP1B3-mediated E3S uptake by EGCG. |
| تدمد: | 1520-5118 0021-8561 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a11eb3cf876b87d33e8a54614d3b590b https://doi.org/10.1021/acs.jafc.2c02692 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a11eb3cf876b87d33e8a54614d3b590b |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15205118 00218561 |
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