title: Exploring the gating mechanisms of aquaporin-3: new clues for the design of inhibitors?
abstract: 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.
authors.affiliation: Dept. of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: de Almeida
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. gsoveral@ff.ulisboa.pt and Dept. Bioquímica e Biologia Humana, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.
authors.forename: A P
authors.initials: AP
authors.lastname: Martins
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. gsoveral@ff.ulisboa.pt and Dept. Bioquímica e Biologia Humana, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.
authors.forename: A F
authors.initials: AF
authors.lastname: Mósca
authors.affiliation: Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Wijma
authors.affiliation: Research Center "Linking Landscape, Environment, Agriculture and Food" (LEAF), Instituto Superior de Agronomia, Universidade de Lisboa, 1349-017 Lisboa, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Prista
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal. gsoveral@ff.ulisboa.pt and Dept. Bioquímica e Biologia Humana, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.
authors.forename: G
authors.initials: G
authors.lastname: Soveral
authors.affiliation: Dept. of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands and School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK. casinia@cardiff.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Casini
mesh_terms: D000818:Animals; D051400:Aquaporin 3 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D003001:Cloning, Molecular; D003198:Computer Simulation; D015195:Drug Design; D015870:Gene Expression; D005990:Glycerol / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D021381:Protein Transport; D051381:Rats
chemical_list: D051400:Aquaporin 3; D005990:Glycerol