Zinc Biochemistry: From a Single Zinc Enzyme to a Key Element of Life
Zinc Biochemistry: From a Single Zinc Enzyme to a Key Element of Life
复制标题
DOI：
10.3945/an.112.003038
复制
发表时间：
2013-01-01
影响因子：
9.3
通讯作者：
Maret, Wolfgang
中科院分区：
文献类型：
--
作者：
Maret, Wolfgang
早在锌生物化学开始之前，人们就认识到锌对生物体生长的营养重要性。锌是在1939年碳酸酐酶中发现的。艰苦的分析工作随后证明了锌作为几百种酶的催化和结构辅助因子的存在。在20世纪80年代，随着“锌指”蛋白的新原理，锌在与其他生物分子相互作用的区域中具有结构功能，该领域再次获得了动力。结构生物学的进步和基因/蛋白质数据库可用性的迅速增加现在使得从序列中检测到的金属结合基序预测锌结合位点成为可能。这一过程导致锌蛋白质组的定义和显著的估计，人类基因组编码类似3000锌蛋白。最近的研究进展集中在锌离子在细胞内和细胞间信息传递中的调节功能，并对锌在信号转导和细胞控制中的其他功能产生了诱人的影响。至少有36种蛋白质稳态控制着锌的囊泡储存和亚细胞分布以及锌离子的浓度。定量研究锌与蛋白质的相互作用强度，以及锌如何被缓冲以控制游离锌（II）离子的显著低细胞和亚细胞浓度，从而产生新的原理。可以公平地得出结论，锌对健康和疾病的影响至少与铁一样深远。中华医学杂志，2013(4):82-91。
The nutritional essentiality of zinc for the growth of living organisms had been recognized long before zinc biochemistry began with the discovery of zinc in carbonic anhydrase in 1939. Painstaking analytical work then demonstrated the presence of zinc as a catalytic and structural cofactor in a few hundred enzymes. In the 1980s, the field again gained momentum with the new principle of "zinc finger" proteins, in which zinc has structural functions in domains that interact with other biomolecules. Advances in structural biology and a rapid increase in the availability of gene/protein databases now made it possible to predict zinc-binding sites from metal-binding motifs detected in sequences. This procedure resulted in the definition of zinc proteomes and the remarkable estimate that the human genome encodes similar to 3000 zinc proteins. More recent developments focus on the regulatory functions of zinc(II) ions in intra- and intercellular information transfer and have tantalizing implications for yet additional functions of zinc in signal transduction and cellular control. At least three dozen proteins homeostatically control the vesicular storage and subcellular distribution of zinc and the concentrations of zinc(II) ions. Novel principles emerge from quantitative investigations on how strongly zinc interacts with proteins and how it is buffered to control the remarkably low cellular and subcellular concentrations of free zinc (II) ions. It is fair to conclude that the impact of zinc for health and disease will be at least as far-reaching as that of iron. Adv. Nutr. 4:82-91, 2013.