Christianson D W
Department of Chemistry, University of Pennsylvania, Philadelphia 19104.
Adv Protein Chem. 1991;42:281-355. doi: 10.1016/s0065-3233(08)60538-0.
The biological function of zinc is governed by the composition of its tetrahedral coordination polyhedron in the metalloprotein, and each ligand group that coordinates to the metal ion does so with a well-defined stereochemical preference. Consequently, protein-zinc recognition and discrimination requires proper chemical composition and proper stereochemistry of the metal-ligand environment. However, it should be noted that the entire protein behaves as the "zinc ligand," since residues that are quite distant from the metal affect recognition and function by through-space (either solvent or the protein milieu) or through-hydrogen bond coulombic interactions. Additionally, long-range interactions across hydrogen bonds serve to orient ligands and therefore minimize the entropy loss incurred on metal binding. Since zinc is not subject to ligand field stabilization effects, it is easy for the tetrahedral protein-binding site to discriminate zinc from other first-row transition metal ions: It is only for Zn2+ that the change from an octahedral to a tetrahedral ligand field is not energetically disfavored. Structural considerations such as these must illuminate the engineering of de novo zinc-binding sites in proteins. Zinc serves chemical, structural, and regulatory roles in biological systems. In biological chemistry zinc serves as an electrophilic catalyst; that is, it stabilizes negative charges encountered during an enzyme-catalyzed reaction. The coordination polyhedron of catalytic zinc is usually dominated by histidine side chains. In biological structure zinc is typically sequestered from solvent, and its coordination polyhedron is almost exclusively dominated by cysteine thiolates. Structural or regulatory zinc is found as either a single metal ion or as part of a cluster of two or more metals. In multinuclear clusters cysteine thiolates either bridge two metal ions or serve as terminal ligands to a single metal ion. Even in complex multinuclear clusters, Zn2+ displays tetrahedral coordination. The structural biology of zinc continues to receive attention in catalytic and regulatory systems such as leucine aminopeptidase, alkaline phosphatase, transcription factors, and steroid receptors. For example, zinc-mediated hormone-receptor association has recently been demonstrated in the binding of human growth hormone to the extracellular binding domain of the human prolactin receptor (Cunningham et al., 1990). To be sure, structural studies of zinc in biology will continue to be a fruitful source of bioinorganic advances, as well as surprises, in the future.
锌的生物学功能由其在金属蛋白中的四面体配位多面体的组成决定，并且每个与金属离子配位的配体基团都具有明确的立体化学偏好。因此，蛋白质与锌的识别和区分需要金属-配体环境具有适当的化学组成和适当的立体化学。然而，应该注意的是，整个蛋白质起着“锌配体”的作用，因为与金属距离很远的残基通过空间（溶剂或蛋白质环境）或通过氢键库仑相互作用影响识别和功能。此外，跨氢键的远程相互作用有助于使配体定向，从而使金属结合时产生的熵损失最小化。由于锌不受配体场稳定化效应的影响，四面体蛋白质结合位点很容易将锌与其他第一排过渡金属离子区分开来：只有对于Zn2+，从八面体配体场到四面体配体场的变化在能量上才是有利的。诸如此类的结构考虑必然会为蛋白质中从头设计锌结合位点提供启示。锌在生物系统中发挥化学、结构和调节作用。在生物化学中，锌用作亲电催化剂；也就是说，它稳定酶催化反应过程中遇到的负电荷。催化锌的配位多面体通常以组氨酸侧链为主。在生物结构中，锌通常与溶剂隔离，其配位多面体几乎完全以半胱氨酸硫醇盐为主。结构或调节锌以单个金属离子或两个或更多金属的簇的一部分的形式存在。在多核簇中，半胱氨酸硫醇盐要么桥接两个金属离子，要么作为单个金属离子的末端配体。即使在复杂的多核簇中，Zn2+也显示四面体配位。锌的结构生物学在诸如亮氨酸氨肽酶、碱性磷酸酶、转录因子和类固醇受体等催化和调节系统中继续受到关注。例如，最近在人生长激素与人催乳素受体的细胞外结合域的结合中证明了锌介导的激素-受体结合（坎宁安等人，1990年）。可以肯定的是，未来对生物锌的结构研究将继续成为生物无机化学进展以及惊喜的丰富来源。
