Kille P, Hemmings A, Lunney E A
Department of Biochemistry, University of Wales College of Cardiff, Wales, UK.
Biochim Biophys Acta. 1994 Apr 13;1205(2):151-61. doi: 10.1016/0167-4838(94)90228-3.
Metallothionein (MT) has provided nature with a small molecule which exhibits multiple facets. The distinct arrangement of cysteine residues which occurs within the two domains of MT confers predisposed metal specificity upon each domain. Furthermore, subtle changes in primary sequence may be built onto the metal cluster scaffold. These not only bestow immunodistinction but may also potentially allow specific members of this family such as MT-III to fulfill unique biological roles. An understanding of how the structures of MT molecules predetermine their biochemical characteristics may allow the design of novel metal-binding molecules specific for the metal ion of choice. Already, using nature as a blueprint, a semi-specific cadmium-binding molecule has been constructed from a polymer of mammalian C-terminal domains. This novel protein has been used to protect tobacco plants from cadmium toxicity. In addition, modeling of biologically active determinants which are located on the external face of MT-III may facilitate the design of small synthetic molecules which mimic the biological activity of MT-III and prevent the distressing effects of memory and speech loss associated with Alzheimer's disease. Memories of metallothionein may yet be something worth remembering!
金属硫蛋白（MT）为自然界提供了一种具有多种特性的小分子。MT两个结构域内半胱氨酸残基的独特排列赋予了每个结构域特定的金属特异性。此外，一级序列的细微变化可能构建在金属簇支架上。这些变化不仅赋予了免疫特异性，还可能使该家族的特定成员（如MT-III）发挥独特的生物学作用。了解MT分子的结构如何预先决定其生化特性，可能有助于设计针对所选金属离子的新型金属结合分子。目前，以自然为蓝图，已经从哺乳动物C端结构域的聚合物构建了一种半特异性镉结合分子。这种新型蛋白质已被用于保护烟草植物免受镉毒性影响。此外，对位于MT-III外表面的生物活性决定簇进行建模，可能有助于设计模仿MT-III生物活性的小分子，从而预防与阿尔茨海默病相关的记忆和言语丧失的痛苦影响。金属硫蛋白的相关研究可能仍值得铭记！
