Arcos-López Trinidad, Schuth Nils, Quintanar Liliana
Met Ions Life Sci. 2020 Mar 23;20. doi: 10.1515/9783110589757-009.
Cupredoxins host in their scaffold one of the most studied and interesting metal sites in biology: the type 1 (T1) or blue Cu center. Blue Cu proteins have evolved to play key roles in biological electron transfer and have the ability to react with a wide variety of redox partners. The inner coordination sphere of T1 Cu sites conserves two histidines and one cysteine with a short Cu-S(Cys) bond as ligands in a trigonal arrangement, with a variable axial ligand that modulates the electronic structure and reactivity. The structural, electronic and geometric features of T1 Cu centers provide the basis for a site that can be optimized by the protein structure for each biological function. This chapter highlights the properties that make this unique Cu center in biology an efficient and tunable electron transfer site. The contributions of the first coordination shell and the high covalency of the Cu-S(Cys) bond in the T1 Cu site to its distinctive geometric and spectroscopic features are discussed, as well as the role of the protein scaffold in imposing an 'entatic' state with a distorted tetrahedral geometry that minimizes geometric changes upon redox cycling. The analysis of naturally occurring perturbed blue Cu sites provides further insights into how the protein scaffold can tune the properties of the T1 Cu site. Blue Cu sites display a wide range of reduction potentials, as these are tuned to be consistent with their physiologically relevant electron donors and acceptors. The different properties of the protein matrix that play important roles in finetuning the reduction potential of T1 Cu sites are also discussed, including the nature of the axial ligand and outer coordination sphere effects. These concepts are further illustrated by the discussion of examples of biosynthetic blue Cu proteins. Finally, the different features of the T1 Cu site that make it an optimal site for electron transfer (ET) are discussed, in terms of Markus theory for intra- and inter-molecular ET. The active site in multicopper oxidases is used as an example to illustrate the contributions of the anisotropic covalency of the blue Cu site to an efficient ET, while the diverse reactivity of the T1 Cu sites in these enzymes is discussed to dissect the different properties provided by the protein that help tune these unique sites for biological ET.
1型（T1）或蓝色铜中心。蓝色铜蛋白在生物电子传递中发挥着关键作用，并且能够与多种氧化还原伙伴发生反应。T1铜位点的内配位层保留了两个组氨酸和一个半胱氨酸，其中短的Cu-S（半胱氨酸）键作为配体呈三角排列，还有一个可变的轴向配体，它调节着电子结构和反应活性。T1铜中心的结构、电子和几何特征为一个可通过蛋白质结构针对每种生物学功能进行优化的位点提供了基础。本章重点介绍了使生物学中这个独特的铜中心成为高效且可调节的电子传递位点的特性。讨论了第一配位层以及T1铜位点中Cu-S（半胱氨酸）键的高共价性对其独特几何和光谱特征的贡献，以及蛋白质支架在施加具有扭曲四面体几何结构的“内稳态”状态方面的作用，这种状态可使氧化还原循环时的几何变化最小化。对天然存在的受扰蓝色铜位点的分析进一步深入了解了蛋白质支架如何调节T1铜位点的特性。蓝色铜位点表现出广泛的还原电位，因为这些电位被调节为与其生理相关的电子供体和受体相一致。还讨论了在微调T1铜位点还原电位方面起重要作用的蛋白质基质的不同特性，包括轴向配体的性质和外配位层效应。通过对生物合成蓝色铜蛋白实例的讨论进一步阐明了这些概念。最后，根据分子内和分子间电子传递的马库斯理论，讨论了使T1铜位点成为电子传递（ET）最佳位点的不同特征。以多铜氧化酶中的活性位点为例，说明蓝色铜位点的各向异性共价性对高效电子传递的贡献，同时讨论这些酶中T1铜位点的不同反应活性，以剖析蛋白质提供的不同特性，这些特性有助于为生物电子传递调节这些独特位点。
