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J Mol Biol. 2006 Oct 6;362(5):925-32. Epub 2006 Jul 28.

Differentiating ligand and inhibitor interactions of a single antiporter.

Author information

1
BIOTEC, University of Technology, 01307 Dresden, Germany.

Abstract

Regulatory mechanisms of ion and solute transporters are in focus of biomedical and biochemical studies and build a key for disease therapies. Inhibition of sodium/proton exchangers efficiently prevents ischemic heart disease and reperfusion development in humans, but molecular mechanisms behind are not clear. Using single-molecule force spectroscopy we observe the binding of the inhibitor 2-aminoperimidine (AP) to sodium/proton antiporters NhaA from Escherichia coli. Deactivating interactions were significantly suppressed at enhanced sodium concentrations of 200 mM as well as in the pH-locked inactive conformation of NhaA. New molecular interactions were quantified and localized within the protein occurring upon a competitive inhibitor binding. The inhibitor, which was targeted and bound to the ligand-binding pocket, altered interactions established at alpha-helix IX. These molecular mechanisms deactivating the antiporter were different to those established upon ligand binding and activation of NhaA.

PMID:
16935297
DOI:
10.1016/j.jmb.2006.07.049
[Indexed for MEDLINE]

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