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Evolution of phosphotriesterase activities of the metallo-β-lactamase family: A theoretical study
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2018-04-06
Hao Zhang, Ling Yang, Long-Fei Yan, Rong-Zhen Liao, Wei-Quan Tian

Metallo-β-lactamase (MβL) is a eubacterial zinc metallo-hydrolase superfamily. Despite their well-known lactamase activities, MβL family members also have the ability to catalyze phosphotriester hydrolysis with different phosphotriesterase activities. In the present study, based on crystal structure comparisons of the related MβL members, a series of models was constructed and calculated using the density functional theory (DFT) method to explore the relationship between active-site changes and phosphotriesterase activities. These calculations show that the energetic barriers for phosphotriesterase activity are considerably reduced due to active-site differences, which describes an evolutionary trend for the development of phosphotriesterase activity in the MβL superfamily. The key event is the appearance of a specialized and negatively charged residue bridging both zinc ions, which plays the two important roles of maintaining charge balance and stabilizing the binuclear active-site structure. This pathway is also consistent with the evolutionary relationships determined by phylogenetic tree analysis using complete residue sequences. Our studies provide the first methodology to explore the development of a new enzyme activity within a superfamily, and to shed new light on understanding the catalytic mechanism from an evolutionary perspective.



中文翻译:

金属β-内酰胺酶家族磷酸三酯酶活性的进化:理论研究

金属β-内酰胺酶(MβL)是真细菌锌金属水解酶超家族。尽管它们具有众所周知的内酰胺酶活性,但MβL家族成员也具有催化具有不同磷酸三酯酶活性的磷酸三酯水解的能力。在本研究中,基于相关MβL成员的晶体结构比较,使用密度泛函理论(DFT)方法构建和计算了一系列模型,以探索活性位点变化与磷酸三酯酶活性之间的关系。这些计算表明,由于活性位点的差异,磷酸三酯酶活性的能量屏障被大大降低,这描述了MβL超家族中磷酸三酯酶活性发展的进化趋势。关键事件是桥接两个锌离子的专用负电荷残基的出现,该残基在保持电荷平衡和稳定双核活性位点结构中起着两个重要作用。该途径也与通过使用完整残基序列的系统树分析所确定的进化关系一致。我们的研究提供了第一个方法来探索超家族中新酶活性的发展,并为从进化的角度理解催化机理提供了新的思路。该途径也与通过使用完整残基序列的系统树分析所确定的进化关系一致。我们的研究提供了第一个方法来探索超家族中新酶活性的发展,并为从进化的角度理解催化机理提供了新的思路。该途径也与通过使用完整残基序列的系统树分析所确定的进化关系一致。我们的研究提供了第一个方法来探索超家族中新酶活性的发展,并为从进化的角度理解催化机理提供了新的思路。

更新日期:2018-04-06
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