title: The mechanism of aquaporin inhibition by gold compounds elucidated by biophysical and computational methods.
abstract: The inhibition of water and glycerol permeation via human aquaglyceroporin-3 (AQP3) by gold(iii) complexes has been studied by stopped-flow spectroscopy and, for the first time, its mechanism has been described using molecular dynamics (MD), combined with density functional theory (DFT) and electrochemical studies. The obtained MD results showed that the most effective gold-based inhibitor, anchored to Cys40 in AQP3, is able to induce shrinkage of pores preventing glycerol and water permeation. Moreover, the good correlation between the affinity of the Au(iii) complex to Cys binding and AQP3 inhibition effects was highlighted, while no influence of the different oxidative character of the complexes could be observed.
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK. casinia@cardiff.ac.uk.
authors.forename: Andreia
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: Andreia F
authors.initials: AF
authors.lastname: Mósca
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK. casinia@cardiff.ac.uk.
authors.forename: Darren
authors.initials: D
authors.lastname: Wragg
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK. casinia@cardiff.ac.uk.
authors.forename: Margot
authors.initials: M
authors.lastname: Wenzel
authors.affiliation: School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, BT9 5AG, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Kavanagh
authors.affiliation: Dip. di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Viale delle Scienze Ed. 17, 90128, Palermo, Italy.
authors.forename: Giampaolo
authors.identifier: http://orcid.org/0000-0001-8773-2359
authors.initials: G
authors.lastname: Barone
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK. casinia@cardiff.ac.uk.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leoni
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: Graça
authors.initials: G
authors.lastname: Soveral
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK. casinia@cardiff.ac.uk.
authors.forename: Angela
authors.identifier: http://orcid.org/0000-0003-1599-9542
authors.initials: A
authors.lastname: Casini
mesh_terms: D051400:Aquaporin 3 / Q000037:antagonists & inhibitors*; D006801:Humans; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D050607:Organogold Compounds / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory
chemical_list: C496027:AQP3 protein, human; D050607:Organogold Compounds; D051400:Aquaporin 3