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Exploring the gating mechanisms of aquaporin-3: new dues for the design of inhibitors?

机译:探索水通道蛋白3的门控机制:抑制剂设计的新契机?

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摘要

The pH gating of human AQP3 and its effects on both water and glycerol permeabilities have been fully characterized for the first time using a human red blood cell model (hRBC). For comparison, the effects of pH on the gating of rat AQP3 have also been characterized in yeast. The obtained results highlight similarities as well as differences between the two isoforms. In addition, we investigated the molecular mechanism of hAQP3 pH gating in silico, which may disclose new pathways to AQP regulation by small molecule inhibitors, and therefore may be important for drug development.
机译:人AQP3的pH门控及其对水和甘油通透性的影响已首次使用人红细胞模型(hRBC)进行了全面表征。为了进行比较,还已经在酵母中表征了pH对大鼠AQP3门控的影响。所得结果突出了两种同工型之间的相似性和差异。此外,我们研究了hAQP3 pH门控的分子机制,该机制可能揭示了小分子抑制剂对AQP进行调控的新途径,因此对于药物开发可能很重要。

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  • 来源
    《Molecular BioSystems》 |2016年第5期|1564-1573|共10页
  • 作者单位

    Dept. of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands;

    Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal,Dept. Bioquimica e Biologia Humana, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal;

    Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal,Dept. Bioquimica e Biologia Humana, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal;

    Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands;

    Research Center 'Linking Landscape, Environment, Agriculture and Food' (LEAF), Instituto Superior de Agronomia, Universidade de Lisboa, 1349-017 Lisboa, Portugal;

    Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal,Dept. Bioquimica e Biologia Humana, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal;

    Dept. of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands,School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK;

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