Beckman Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Beckman Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
J Inorg Biochem. 2022 Sep;234:111886. doi: 10.1016/j.jinorgbio.2022.111886. Epub 2022 Jun 2.
The SARS-CoV-2 main protease (M) is responsible for cleaving twelve nonstructural proteins from the viral polyprotein. M, a cysteine protease, is characterized by a large number of noncatalytic cysteine (Cys) residues, none involved in disulfide bonds. In the absence of a tertiary-structure stabilizing role for these residues, a possible alternative is that they are involved in redox processes. We report experimental work in support of a proposal that surface cysteines on M can protect the active-site Cys145 from oxidation by reactive oxygen species (ROS). In investigations of enzyme kinetics, we found that mutating three surface cysteines to serines did not greatly affect activity, which in turn indicates that these cysteines could protect Cys145 from oxidative damage.
严重急性呼吸综合征冠状病毒 2 主蛋白酶（M）负责从病毒多蛋白中切割出 12 种非结构蛋白。M 是一种半胱氨酸蛋白酶，其特征是含有大量非催化半胱氨酸（Cys）残基，没有一个参与二硫键的形成。在这些残基没有稳定三级结构的作用的情况下，它们可能参与氧化还原过程。我们报告了支持以下假设的实验工作，即 M 上的表面半胱氨酸可以保护活性位点 Cys145 不被活性氧（ROS）氧化。在对酶动力学的研究中，我们发现将三个表面半胱氨酸突变为丝氨酸并没有大大影响活性，这反过来表明这些半胱氨酸可以保护 Cys145 免受氧化损伤。
