PHYSICS OF IONIC CHANNELS AND OTHER PROTEINS WITH AQUEOUS CAVITIES

在调节血红蛋白氧亲和力的“变构效应物”中， 长期以来已知氯离子具有显著的生理毒性， 作用 从O2结合和C1- 活性，据认为，一些1.6氯化物结合，以稳定 “脱氧”或“T”形式[1-4]。 去年我们发现氧气 血红蛋白的亲和力与存在下的进食者活动相关， 几种中性溶质。 我们推断， 脱氧T状态到完全氧化R状态的转变约为60 - 65 沃茨。 于是，我们不得不问，盐是否具有渗透性， 副作用类似于中性溶质。 因此，我们重新- 研究了氯化物的调节作用，明确包括 蛋白质水合作用和水活度对添加盐的依赖性。 我们 现在发现数据的替代描述只有一个 变构氯离子（Δ c1 = -1.22 +0.02 C1-）直接与 在脱氧到氧过渡期间的氧合，而一些65.2 ± 2.4 额外的水分子与蛋白质结合[（5）]。 在这 分析，C1-调节负载的四个氧可以描述为 反应式为：Hb.C1 + 4 O2 + 65 H2O <==> Hb.4O2.65H2O + C1-。 远比血红蛋白或氯化物本身更重要的是，我们 现在必须面对的可能性，在衡量行动的一般偏见， 蛋白质功能的“效应子”，忽略溶剂化的偏差， 新的水化力似乎在生物分子中无处不在。

Among the "allosteric effectors" regulating Hemoglobin oxygen affinity, chloride ions have long been known to have a significant physiological role. From in vitro studies of the relation between O2 binding and C1- activity, it has been thought that some 1.6 Chlorides bind to stabilize the "deoxy" or "T" form [1-4]. Last year we discovered that the oxygen affinity of Hemoglobin correlates with eater activity in the presence of several neutral solutes. We inferred a change in protein hydration in the deoxy T state to fully oxygenated R state transition of some 60 - 65 waters. We were forced to ask, then, whether salt could have an osmotic side-effect similar to that seen with neutral solutes. We therefore re- examined the regulatory action of chloride, explicitly including changes in protein hydration and the dependence of water activity on added salt. We now find that an alternate description of the data has only a single allosteric chloride ion (delta c1 = -1.22 + 0.02 C1-) directly linked with oxygenation during the deoxy-to-oxy transition, while some 65.2 + 2.4 additional water molecules bind to the protein [ (5)]. Within this analysis, the C1- -regulated loading of four oxygens can be described by the reaction, Hb.C1 + 4O2 + 65H2O <==> Hb.4O2.65H2O + C1-. Far more important than simply a matter of Hemoglobin or chloride alone, we must now face the possibility of a general bias in gauging the action of "effectors" of protein function, a bias from neglect of solvation and the new hydration forces that seem to be ubiquitous among bio-molecules.