Critical Role of Water in the Binding of Volatile Anesthetics to Proteins

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• 作者：Hai-Jing Wang ; Alfred Kleinhammes ; Pei Tang ; Yan Xu ; Yue Wu
• 刊名：Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：October 10, 2013
• 年：2013
• 卷：117
• 期：40
• 页码：12007-12012
• 全文大小：311K
• 年卷期：v.117,no.40(October 10, 2013)
• ISSN：1520-5207

文摘

Numerous small molecules exhibit drug-like properties by low-affinity binding to proteins. Such binding is known to be influenced by water, the detailed picture of which, however, remains unclear. One particular example is the controversial role of water in the binding of general anesthetics to proteins as an essential step in general anesthesia. Here we demonstrate that a critical amount of hydration water is a prerequisite for anesthetic鈥損rotein binding. Using nuclear magnetic resonance, the concurrent adsorption of hydration water and bound anesthetics on model proteins are simultaneously measured. Halothane binding on proteins can only take place after protein hydration reaches a threshold hydration level of 0.31 g of water/g of proteins at the relative water vapor pressure of 0.95. Similar dependence on hydration is also observed for several other anesthetics. The ratio of anesthetic partial pressures at which two different anesthetics reach the same fractional load is correlated with the anesthetic potency. The binding of nonimmobilizers, which are structurally similar to known anesthetics but unable to produce anesthesia, does not occur even after the proteins are fully hydrated. Our results provide the first unambiguous experimental evidence that water is absolutely required to enable anesthetic鈥損rotein interactions, shedding new light on the general mechanism of molecular recognition and binding.