The inhibition of glycerol permeation through aquaglyceroporin-3 induced by mercury(II)

6533b821fe1ef96bd127c35c

RESEARCH PRODUCT

The inhibition of glycerol permeation through aquaglyceroporin-3 induced by mercury(II)

Andreia De Almeida Angela Casini Angela Casini Angelo Spinello Giampaolo Barone

subject

Glycerol 0301 basic medicine Molecular dynamic Cell Membrane Permeability Biochemistry Protein Structure Secondary chemistry.chemical_compound GLPF COORDINATION CRYSTAL Escherichia coli Proteins Permeation Biochemistry Covalent bond Settore CHIM/03 - Chimica Generale E Inorganica Phosphatidylcholines COMPLEXES Protein Binding STRUCTURAL BASIS Cations Divalent Plasmodium falciparum Aquaporin CYSTEINE-189 Molecular Dynamics Simulation Molecular dynamics Aquaporins WATER CHANNEL Inorganic Chemistry 03 medical and health sciences Escherichia coli Glycerol Extracellular Humans Molecule PERMEABILITY Protein Structure Quaternary Aquaporin 3 Binding Sites AQUAPORIN INHIBITION Water Biological Transport Membranes Artificial Aquaglyceroporin Mercury SIMULATIONS Protein Structure Tertiary Cytosol Water permeation 030104 developmental biology Aquaglyceroporins chemistry Structural Homology Protein Biophysics Glycerol permeation

description

Mercurial compounds are known to inhibit water permeation through aquaporins (AQPs). Although in the last years some hypotheses were proposed, the exact mechanism of inhibition is still an open question and even less is known about the inhibition of the glycerol permeation through aquaglyceroporins. Molecular dynamics (MD) simulations of human aquaporin-3 (AQP3) have been performed up to 200 ns in the presence of Hg2+ ions. For the first time, we have observed the unbiased passage of a glycerol molecule from the extracellular to cytosolic side. Moreover, the presence of Hg2+ ions covalently bound to Cys40 leads to a collapse of the aromatic/arginine selectivity filter (ar/R SF), blocking the passage of both glycerol and water. Interestingly, the local conformational changes of the protein follow mercury coordination by water and by aminoacidic donor atoms. Overall, the obtained results are important to improve the design of selective AQP inhibitors for future therapeutic and imaging applications. (C) 2015 Elsevier Inc. All rights reserved.

year	journal	country	edition	language
2016-07-01	Journal of Inorganic Biochemistry

10.1016/j.jinorgbio.2015.11.027 https://doi.org/10.1016/j.jinorgbio.2015.11.027