Faculty of Chemistry and Pharmacy, Sofia University, Sofia 1164, Bulgaria.
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
J Phys Chem B. 2021 Sep 23;125(37):10419-10431. doi: 10.1021/acs.jpcb.1c05154. Epub 2021 Sep 13.
Divalent calcium ion (Ca) plays an indispensable role as a second messenger in a myriad of signal transduction processes. Of utmost importance for the faultless functioning of calcium-modulated signaling proteins is their binding selectivity of the native metal cation over rival biogenic/abiogenic metal ion contenders in the intra/extracellular fluids. In this Perspective, we summarize recent findings on the competition between the cognate Ca and other biogenic or abiogenic divalent cations for binding to Ca-signaling proteins or organic cofactors. We describe the competition between the two most abundant intracellular biogenic metal ions (Mg and Ca) for Ca-binding sites in signaling proteins, followed by the rivalry between native Ca and "therapeutic" Li as well as "toxic" Pb. We delineate the key factors governing the rivalry between the native and non-native cations in proteins and highlight key implications for the biological performance of the respective proteins/organic cofactors.
二价钙离子 (Ca) 在无数信号转导过程中作为第二信使起着不可或缺的作用。对于钙调节信号蛋白的正常功能至关重要的是，它们在细胞内外液中对天然金属阳离子的结合选择性，超过竞争的生物/非生物金属离子竞争者。在这篇观点文章中，我们总结了最近关于同型 Ca 和其他生物或非生物二价阳离子与钙信号蛋白或有机辅因子结合的竞争的发现。我们描述了两种最丰富的细胞内生物金属离子 (Mg 和 Ca) 之间在信号蛋白中的 Ca 结合位点的竞争，然后是天然 Ca 与“治疗性”Li 以及“毒性”Pb 之间的竞争。我们描述了控制蛋白质中天然和非天然阳离子竞争的关键因素，并强调了对各自蛋白质/有机辅因子的生物学性能的关键影响。
