Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 362, Issue 5, Pages 925-932Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2006.07.049
Keywords
atomic force microscopy; molecular interactions; NhaA; inactivation
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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 ischernic 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. (c) 2006 Elsevier Ltd. All rights reserved.
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