Departments of Biochemistry and Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9NH, UK.
J Inorg Biochem. 2024 Feb;251:112431. doi: 10.1016/j.jinorgbio.2023.112431. Epub 2023 Nov 19.
Metal sites in proteins are often presented in an idealized way that does not capture the intrinsic dynamic behavior of the protein or the extrinsic factors that affect changes in the coordination of the metal ion in biological space and time. The bioinorganic chemistry possible in healthy and diseased living organisms is limited by prevailing pH values, redox potentials, and availability and concentrations of metal ions and ligands. Changes in any of these parameters and protein-protein or protein-ligand interactions can result in differences in the type of metal ion bound, metal occupancy, and coordination number or geometry. This article addresses the plasticity and complexity of metal coordination in proteins when these parameters are considered. It uses three examples of zinc sites with sulfur donor atoms from cysteines in mammalian proteins: alcohol dehydrogenases, metallothioneins, and zinc transporters of the ZnT (SLC30A) family. Coordination dynamics of the metal sites in these proteins has different purposes; in alcohol dehydrogenases for the metal ion to perform its different roles in the catalytic cycle, in metallothioneins for serving as a metal buffer, and in ZnT zinc transporters for sensing metal ions and moving them through the protein and thus biological membranes. Defining the biological and chemical parameters that determine and affect coordination dynamics of metal ions in proteins will inform future investigations of metalloproteins.
蛋白质中的金属位点通常以理想化的方式呈现，无法捕捉蛋白质的固有动态行为或影响生物空间和时间内金属离子配位变化的外在因素。在健康和患病的生物体中进行的生物无机化学受到普遍存在的 pH 值、氧化还原电位以及金属离子和配体的可用性和浓度的限制。这些参数中的任何一个变化以及蛋白质-蛋白质或蛋白质-配体相互作用都可能导致结合的金属离子类型、金属占有率以及配位数或几何形状发生变化。本文讨论了在考虑这些参数时蛋白质中金属配位的可变性和复杂性。它使用了哺乳动物蛋白质中来自半胱氨酸的硫供体原子的三个锌位点的例子：醇脱氢酶、金属硫蛋白和 ZnT（SLC30A）家族的锌转运蛋白。这些蛋白质中金属位点的配位动力学具有不同的目的；在醇脱氢酶中，金属离子在催化循环中发挥不同的作用，在金属硫蛋白中作为金属缓冲剂，在 ZnT 锌转运蛋白中作为金属离子传感器并将其穿过蛋白质和生物膜。定义决定和影响蛋白质中金属离子配位动力学的生物学和化学参数将为未来对金属蛋白的研究提供信息。
