Institut for Physics, University of Greifswald, Germany; Institute for Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Germany.
Institute for Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Germany.
Redox Biol. 2023 Sep;65:102832. doi: 10.1016/j.redox.2023.102832. Epub 2023 Jul 29.
Redox modifications of specific cysteinyl and methionyl residues regulate key enzymes and signal-transducing proteins in various pathways. Here, we analyzed the effect of redox modifications on protein structure screening the RCSB protein data bank for oxidative modifications of proteins, i.e. protein disulfides, mixed disulfides with glutathione, cysteinyl sulfenic acids, cysteinyl S-nitrosylation, and methionyl sulfoxide residues. When available, these structures were compared to the structures of the same proteins in the reduced state with respect to both pre-requirements for the oxidative modifications as well as the structural consequences of the modifications. In general, the conformational changes induced by the redox modification are small, i.e. within the range of normal fluctuations. Some redox modifications, disulfides in particular, induces alterations in the electrostatic properties of the proteins. Solvent accessibility does not seem to be a strict pre-requirement for the redox modification of a particular residue. We identified an enrichment of certain other amino acid residues in the vicinity of the susceptible residues, for disulfide and sulfenic acid modifications, for instance, histidyl and tyrosyl residues. These motifs, as well as the specific features of the susceptible sulfur-containing amino acids, may become helpful for the prediction of redox modifications.
特定半胱氨酸和甲硫氨酸残基的氧化还原修饰调节各种途径中的关键酶和信号转导蛋白。在这里，我们分析了氧化还原修饰对蛋白质结构的影响，通过筛选 RCSB 蛋白质数据库中蛋白质的氧化修饰，即蛋白质二硫键、与谷胱甘肽的混合二硫键、半胱氨酸亚磺酸、半胱氨酸 S-亚硝酰化和甲硫氨酸亚砜残基。在可用的情况下，将这些结构与同一蛋白质的还原状态下的结构进行比较，同时考虑到氧化修饰的先决条件以及修饰的结构后果。一般来说，氧化还原修饰引起的构象变化很小，即在正常波动范围内。一些氧化还原修饰，特别是二硫键，会改变蛋白质的静电特性。溶剂可及性似乎不是特定残基氧化还原修饰的严格先决条件。我们确定了在易受影响的残基附近存在某些其他氨基酸残基的富集，例如二硫键和亚磺酸修饰的组氨酸和酪氨酸残基。这些基序以及易受影响的含硫氨基酸的特定特征可能有助于预测氧化还原修饰。
