Roesijadi G
University of Maryland Center for Environmental Science, Chesapeake Biological Laboratory, Solomons 20688, USA.
Cell Mol Biol (Noisy-le-grand). 2000 Mar;46(2):393-405.
High kinetic reactivity and high metal affinity of the metal-binding sites of metallothionein are characteristics that would facilitate involvement of the thionein-zinc metallothionein couple in metal transfer or exchange reactions. Studies demonstrating thionein-metallothionein-mediated activation or inhibition of various zinc metalloenzymes and transcription factors provide support for a potential role for metallothionein in metal transfer reactions with receptor molecules. Although a role in basal zinc regulation is currently a topic of debate, less controversial is a role for metallothionein in the detoxification of metals such as cadmium. The toxicity of metals can, in part, be due to adventitious binding to charged sites of target proteins or the displacement of zinc bound to zinc metalloproteins. Zinc metallothionein has the capability of repairing such structures through abstraction of a toxic metal in the former case or through a reciprocal metal transfer reaction that involves abstraction of the toxic metal and donation of the essential metal zinc in the latter. This would confer on metallothionein an active role in the protective response to metal toxicity, rather than a passive one that is solely dependent on the high metal affinity for binding free metal ions. The efficacy of such a mechanism for metal detoxification has been demonstrated with enzymes, actin and zinc finger proteins. With zinc finger proteins, zinc metallothionein can restore both altered secondary structure and inhibited DNA-binding function to functional states through a zinc for cadmium exchange.
金属硫蛋白的金属结合位点具有高动力学反应活性和高金属亲和力，这些特性有助于硫蛋白 - 锌金属硫蛋白对参与金属转移或交换反应。多项研究表明，硫蛋白 - 金属硫蛋白可介导多种锌金属酶和转录因子的激活或抑制，这为金属硫蛋白在与受体分子的金属转移反应中发挥潜在作用提供了支持。尽管金属硫蛋白在基础锌调节中的作用目前仍存在争议，但它在镉等金属的解毒过程中发挥作用这一点争议较小。金属的毒性部分可能源于其与靶蛋白带电位点的偶然结合，或锌从锌金属蛋白上的置换。在前一种情况下，锌金属硫蛋白能够通过夺取有毒金属来修复此类结构；在后一种情况下，它则通过一种相互的金属转移反应来修复，该反应包括夺取有毒金属并提供必需金属锌。这将赋予金属硫蛋白在对金属毒性的保护反应中发挥积极作用，而不是仅仅依赖于对游离金属离子的高金属亲和力的被动作用。这种金属解毒机制的有效性已在酶、肌动蛋白和锌指蛋白中得到证实。对于锌指蛋白，锌金属硫蛋白可通过锌 - 镉交换将改变的二级结构和受抑制的DNA结合功能恢复到功能状态。
