6533b7d7fe1ef96bd1268579
RESEARCH PRODUCT
The mechanism of aquaporin inhibition by gold compounds elucidated by biophysical and computational methods
Giampaolo BaroneAndreia De AlmeidaDarren WraggStefano LeoniGraça SoveralAndreia F. MóscaPaul KavanaghMargot N. WenzelAngela Casinisubject
Surfaces Coatings and FilmAquaporinCeramics and CompositeOxidative phosphorylationMolecular Dynamics Simulation010402 general chemistryElectrochemistry01 natural sciencesCatalysisCatalysiMolecular dynamicschemistry.chemical_compoundGold CompoundsJournal ArticleMaterials ChemistryGlycerolHumansOrganic chemistryAquaporin 3Molecular Structure010405 organic chemistryChemistryElectronic Optical and Magnetic MaterialChemistry (all)Metals and AlloysGeneral ChemistryPermeation0104 chemical sciencesSurfaces Coatings and FilmsElectronic Optical and Magnetic MaterialsSettore CHIM/03 - Chimica Generale E InorganicaCeramics and CompositesBiophysicsQuantum TheoryDensity functional theoryOrganogold Compoundsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-04-07 | Chemical Communications |