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铜是构成多种酶成分所必需的一种微量元素 ,是维持生命所必需的。但铜过量对人体有很大的毒性。就有关正常铜吸收、细胞内转运及其毒性作一介绍。肝豆状核变性是一种遗传性的铜转运失调 ,引发铜在组织中的蓄积 (如肝脏和脑 ) ,从而导致进行性的肝脏和神经系统损害。肝豆状核变性致病基因编码是公认的铜转运 P-型 ATP酶。该酶最重要特征之一就是存在一个大的 N-末端区域。该区域包括 6个重要的铜结合基序 ,一般认为这些基序负责先结合铜然后使其通过膜。经克隆 ,表达并提纯了肝豆状核变性中 ATP酶的 N-末端区域 (大约 70kd)。该区域的金属结合特性显示出该结合蛋白可结合除铜之外的几种金属 ,但铜对此区域的亲和力较高。铜以一价形式结合于该区域 ,铜与蛋白结合比率为 6.5∶ 1。X线吸收光谱研究证明 ,铜结合于半胱氨酸残基上。园二色性光谱分析表明 ,铜结合于该区域时 ,其 2级和 3级结构变化。铜结合研究表明 ,在结合铜的过程中存在一定程度的协同性。这些研究和详细的铜结合域的结构信息在确定铜转运 ATP酶在体内自身稳定调控作用和 ATP酶基因突变阻断铜运输方面是极其重要的
Copper is a trace element necessary to form a variety of enzyme components, is necessary to maintain life. However, excessive copper on the human body has a lot of toxicity. On the normal copper absorption, intracellular transport and toxicity for an introduction. Hepatolenticular degeneration is an inherited disorder of copper transport, triggering the accumulation of copper in tissues such as the liver and brain, leading to progressive liver and nervous system damage. Wilson’s disease gene mutation coding gene is recognized as copper transport P-type ATPase. One of the most important features of this enzyme is the presence of a large N-terminal region. This region includes six important copper-binding motifs that are thought to be responsible for binding copper first and then passing it through the membrane. The N-terminal region of the ATPase in hepatolenticular degeneration (approximately 70 kd) was cloned, expressed and purified. The metal-binding properties of this region show that the binding protein can bind to several metals other than copper, but copper has a higher affinity for this region. Copper is monovalently bound to this region with a copper to protein binding ratio of 6.5: 1. X-ray absorption spectroscopy studies have shown that copper binds to cysteine residues. The dichroism spectral analysis of the park shows that when the copper is combined in this region, the second- and third-order structures change. Copper bonding studies show that there is some degree of synergy in the copper bonding process. The structural and structural information of these studies and detailed copper-binding domains is of paramount importance in determining the intrinsic stabilizing effects of copper transport ATPase in vivo and mutations in the ATPase gene that block copper transport