We have investigated the structural stability of the SARS (Severe acute respiratory syndrome)-CoV-2 main protease monomer (Mpro). We quantified the spatial and angular changes in the structure using two independent analyses, one based on a spatial metrics (δ, ratio), the second on angular metrics. The order of unfolding of the 10 helices in Mpro is characterized by beta vs alpha plots similar to those of cytochromes and globins. The longest turning region is anomalous in the earliest stage of unfolding. In an investigation of excluded-volume effects, we found that the maximum spread in average molecular-volume values for Mpro, cytochrome c-b₅₆₂, cytochrome c’, myoglobin, and cytoglobin is ~10 Å³. This apparent universality is a consequence of the dominant contributions from six residues: ALA, ASP, GLU, LEU, LYS and VAL. Of the seven Mpro histidines, residues 41, 163, 164, and 246 are in stable H-bonded regions; metal ion binding to one or more of these residues could break up the H-bond network, thereby affecting protease function. Our analysis also indicated that metal binding to cysteine residues 44 and 145 could disable the enzyme.

我们已经研究了SARS（严重急性呼吸综合征）-CoV-2主要蛋白酶单体（Mpro）的结构稳定性。我们使用两个独立的分析来量化结构中的空间和角度变化，一个基于空间量度（δ，比率），第二个基于角度量度。Mpro中10个螺旋的展开顺序以与细胞色素和球蛋白相似的β对α图为特征。最长的转向区域在展开的最早阶段是异常的。在排除体积效果的调查，我们发现，在MPRO，细胞色素均分子量体积值中的最大传播Ç -b ₅₆₂，细胞色素c ^ ”，肌红蛋白，和细胞珠蛋白是〜10埃³。这种明显的普遍性是六个残基的主要贡献的结果：ALA，ASP，GLU，LEU，LYS和VAL。在七个Mpro组氨酸中，残基41、163、164和246位于稳定的H键合区域；与一个或多个这些残基结合的金属离子可能会破坏H键网络，从而影响蛋白酶的功能。我们的分析还表明，金属与半胱氨酸残基44和145的结合可以使酶失活。