Is TEA an inhibitor for human Aquaporin-1?

Excessive water uptake through aquaporins can be life threatening, and disregulation of water permeability causes many diseases. Therefore, reversible aquaporin inhibitors are highly desired. In this paper, we identified the binding site for tetraethylammonium (TEA) of the membrane water channel aquaporin-1 by a combined molecular docking and molecular dynamics simulation approach. The binding site identified from docking studies was independently confirmed with an unbiased molecular dynamics simulation of an aquaporin tetramer embedded in a lipid membrane, surrounded by a 100-mM tetraethylammonium solution in water. A third independent assessment of the binding site was obtained by umbrella sampling simulations. These simulations, in addition, revealed a binding affinity of more than 17 kJ/mol, corresponding to an IC50 value of << 3 mM. Finally, we observed in our simulations a 50% reduction of the water flux in the presence of TEA, in agreement with water permeability measurements on aquaporin expressed in oocytes. These results confirm TEA as a putative lead for an aquaporin-1 inhibitor.

• Publication year

  2008

• Venue

  Pflügers Archiv: European Journal of Physiology

• Publication date

  2008-01-15

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1007/s00424-007-0422-0PMID 18196268PMCID 2756347
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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