钙和镁离子与蛋白质的结合对于调节心脏收缩至关重要。然而,其他二价阳离子,包括外源性物质,可以在心肌中积累并进入心肌细胞,它们可以与蛋白质结合。在这篇文章中,我们总结了这些阳离子对肌球蛋白ATP酶活性和EF-手蛋白的影响,特别注意有毒阳离子。与EF手蛋白的最佳结合发生在接近Mg2和Ca2的离子半径处。在骨骼肌钙蛋白C中,Cd2+,Sr2+,Pb2+,Mn2+,Co2+,Ni2+,Ba2+,Mg2+,Zn2+,三价镧系元素可以代替Ca2+。由于肌球蛋白ATP酶不是特定的MgATP酶,Ca2+,Fe2+,Mn2+,Ni2+,Sr2+可以支持肌球蛋白ATP酶的活性。另一方面,Zn2+和Cu2显著抑制ATPase活性。对各种二价阳离子的亲和力取决于某些蛋白质或其同种型,并且可以随着氨基酸取代和翻译后修饰而改变。心脏EF-手蛋白和肌球蛋白ATP结合口袋是潜在的分子靶毒性阳离子,这可以在分子水平上显著改变心肌的机械特性。
The binding of calcium and magnesium ions to proteins is crucial for regulating heart contraction. However, other divalent cations, including xenobiotics, can accumulate in the myocardium and enter cardiomyocytes, where they can bind to proteins. In this article, we summarized the impact of these cations on myosin ATPase activity and EF-hand proteins, with special attention given to toxic cations. Optimal binding to EF-hand proteins occurs at an ionic radius close to that of Mg2+ and Ca2+. In skeletal Troponin C, Cd2+, Sr2+, Pb2+, Mn2+, Co2+, Ni2+, Ba2+, Mg2+, Zn2+, and trivalent lanthanides can substitute for Ca2+. As myosin ATPase is not a specific MgATPase, Ca2+, Fe2+, Mn2+, Ni2+, and Sr2+ could support myosin ATPase activity. On the other hand, Zn2+ and Cu2 significantly inhibit ATPase activity. The affinity to various divalent cations depends on certain proteins or their isoforms and can alter with amino acid substitution and post-translational modification. Cardiac EF-hand proteins and the myosin ATP-binding pocket are potential molecular targets for toxic cations, which could significantly alter the mechanical characteristics of the heart muscle at the molecular level.