Maret Wolfgang
Division of Human Nutrition, Departments of Preventive Medicine & Community Health and Anesthesiology, University of Texas Medical Branch, 700 Harborside Drive, Galveston, TX 77555, USA.
J Trace Elem Med Biol. 2005;19(1):7-12. doi: 10.1016/j.jtemb.2005.02.003.
Estimates of the number of zinc proteins in humans are now possible and a functional annotation of the zinc proteome can begin. The catalytic and structural roles of zinc in hundreds of enzymes and thousands of so-called "zinc finger" protein domains have provided a molecular basis for the numerous biological functions of this essential element. Additional, regulatory functions of zinc/protein interactions are being recognized. They include roles of the zinc ion in signal transduction, in controlling the architecture of protein complexes, and in redox-active zinc sites, where the binding and release of zinc is under redox control. Moreover, a considerable number of proteins participate in cellular zinc homeostasis, e.g. membrane transporters, and cellular storage, sensor, and trafficking proteins. These proteins have evolved with mechanisms to handle zinc ions rather specifically and selectively. They perform their functions with a remarkably modest set: One redox state of the zinc ion and nitrogen, oxygen, and sulfur ligands from the side chains of histidine, glutamate/aspartate, and cysteine, respectively. By permutation of the ligands in this set, the functional potential of the zinc ion has been fully explored. Different coordination environments modulate the chemical characteristics of the zinc ion, control the kinetics of its binding, and allow it to be either metabolically active or inert. Insights into all these functions are building an understanding of why zinc is so critical for such a multitude of life processes.
现在可以估算出人类锌蛋白的数量了,锌蛋白质组的功能注释工作也能够启动。锌在数百种酶和数千个所谓“锌指”蛋白结构域中发挥的催化和结构作用,为这种必需元素的众多生物学功能提供了分子基础。此外,锌与蛋白质相互作用的调节功能也逐渐被认识到。这些功能包括锌离子在信号转导、控制蛋白质复合物结构以及氧化还原活性锌位点中的作用,在氧化还原活性锌位点中,锌的结合和释放受氧化还原控制。此外,相当数量的蛋白质参与细胞锌稳态,例如膜转运蛋白以及细胞储存、传感和运输蛋白。这些蛋白质进化出了相当特异且有选择性地处理锌离子的机制。它们通过一组非常适度的方式来发挥功能:锌离子的一种氧化态,以及分别来自组氨酸、谷氨酸/天冬氨酸和半胱氨酸侧链的氮、氧和硫配体。通过对这组配体进行排列组合,锌离子的功能潜力得到了充分发掘。不同的配位环境调节锌离子的化学特性,控制其结合动力学,并使其具有代谢活性或惰性。对所有这些功能的深入了解,正在增进人们对锌为何对众多生命过程如此关键的理解。