کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2188855 | 1096188 | 2006 | 8 صفحه PDF | دانلود رایگان |
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 α-helix IX. These molecular mechanisms deactivating the antiporter were different to those established upon ligand binding and activation of NhaA.
Journal: Journal of Molecular Biology - Volume 362, Issue 5, 6 October 2006, Pages 925–932