Matrix metalloproteinase (MMP) is a class of metalloenzyme that cleaves peptide bonds in extracellular matrices. Their functions are important in both health and disease of animals. Here using quantum mechanics simulations of the MMP8 protein, the coordination chemistry of different metal cofactors is examined. Comparisons found that Jhan-Teller effects in Cu(II) destabilize the wild-type MMP8 but a histidine to glutamine mutation at residue number 197 can potentially allow the MMP8 protein to utilize Cu(II) in reactions. Simulations also demonstrates the requirement of a conformational change in the ligand before enzymatic cleavage. The insights provided in here will assist future protein engineering efforts utilizing the MMP8 protein.

中文翻译：

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基质金属蛋白酶8的金属选择性的计算分析

基质金属蛋白酶（MMP）是一类金属酶，可裂解细胞外基质中的肽键。它们的功能在动物的健康和疾病中都很重要。在这里使用MMP8蛋白的量子力学模拟，检查了不同金属辅因子的配位化学。比较发现，Jhan-Teller对Cu（II）的作用破坏了野生型MMP8的稳定性，但是在第197位残基的组氨酸至谷氨酰胺突变可能使MMP8蛋白在反应中利用Cu（II）。模拟还证明了在酶促裂解之前需要改变配体的构象。此处提供的见解将有助于将来利用MMP8蛋白进行蛋白质工程研究。