HUN-REN-UD Mechanisms of Complex Homogeneous and Heterogeneous Chemical Reactions Research Group, Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, H-4032 Debrecen, Hungary.
Doctoral School of Chemistry, University of Debrecen, Debrecen H-4032, Hungary.
Dalton Trans. 2024 Jan 23;53(4):1648-1656. doi: 10.1039/d3dt03638c.
Superoxide dismutase (SOD) enzymes are pivotal in regulating oxidative stress. In order to model Ni containing SOD enzymes, the results of the thermodynamic, spectroscopic and SOD activity studies on the complexes formed between nickel(II) and a NiSOD related peptide, CysCysAspLeuProCysGlyValTyr-NH (), are reported. Cysteine was introduced to replace the first histidine residue in the amino acid sequence of the active site of the NiSOD enzyme. The novel peptide exhibits 3 times higher metal binding affinity compared to the native NiSOD fragment. This is due to the presence of the first cysteine in the coordination sphere of nickel(II). At physiological pH, the (NH,S,S,S) coordinated complex is the major species. This coordination mode is altered when one thiolate group is replaced by an amide nitrogen of the peptide backbone above pH 7.5. The nickel complexes of exhibit similar SOD activity to that of the complex formed with the active site fragment of the native NiSOD. The reaction between the complexes and the superoxide anion was studied by the sequential stopped-flow method. These studies revealed that the nickel(II) complex is always in excess over the nickel(III) complex during the dismutation process. However, the nickel(III) species is also involved in a relatively fast degradation process. This unambiguously proves that a protective mechanism must be operative in the NiSOD enzyme which prevents the oxidation of the sulfur atom of cysteine in the presence of O. The results provide new possibilities for the use of NiSOD mimics in bio- and industrial catalytic processes.
超氧化物歧化酶（SOD）在调节氧化应激中起着关键作用。为了模拟含镍的 SOD 酶，报道了镍（II）与 NiSOD 相关肽 CysCysAspLeuProCysGlyValTyr-NH（）形成的配合物的热力学、光谱和 SOD 活性研究结果。半胱氨酸被引入以取代 NiSOD 酶活性位点氨基酸序列中的第一个组氨酸残基。与天然 NiSOD 片段相比，新肽具有高 3 倍的金属结合亲和力。这是由于镍（II）的配位球中存在第一个半胱氨酸。在生理 pH 下，（NH，S，S，S）配位配合物是主要物种。当一个硫醇基团被肽骨架上的酰胺氮取代时，这种配位模式在 pH 高于 7.5 时发生改变。表现出与天然 NiSOD 活性位点片段形成的配合物相似的 SOD 活性。通过连续停流法研究了配合物与超氧阴离子之间的反应。这些研究表明，在歧化过程中，镍（II）配合物始终过量于镍（III）配合物。然而，镍（III）物种也参与了相对较快的降解过程。这明确证明了 NiSOD 酶中必须存在一种保护机制，以防止在存在 O 的情况下半胱氨酸的硫原子被氧化。研究结果为 NiSOD 模拟物在生物和工业催化过程中的应用提供了新的可能性。
