Molecular dynamics simulations of the mononuclear zinc-beta-lactamase from Bacillus cereus.
Molecular dynamics simulations of the mononuclear zinc-beta-lactamase from Bacillus cereus.
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DOI：
10.1021/ja003796a
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发表时间：
2001-03
影响因子：
15
通讯作者：
D. Suárez;K. Merz
中科院分区：
文献类型：
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作者：
D. Suárez;K. Merz
在此，我们报告了蜡样芽孢杆菌-β-内酰胺酶单核形式的分子动力学模拟。我们研究了两种不同的构型，它们的不同之处在于锌结合氢氧化物或锌结合水的存在以及基本 His210 残基的质子化状态。 MD 分析表征了催化重要残基（Asp90、His210、Cys168 等）与锌中心的接触。通过簇模型上的 QM 计算研究了连接两种构型的 Zn-OH(2) --> His210 质子转移途径的性质，同时通过酶中的 QM/MM 计算估计了两种构型的相对稳定性。根据这些结果，提出了蜡样芽孢杆菌金属酶的动力学活性形式的理论模型。还讨论了 Cys168 残基突变的一些机制含义和影响。
Herein, we report molecular dynamics simulations of the mononuclear form of the Bacillus cereuszinc-beta-lactamase. We studied two different configurations which differ in the presence of a zinc-bound hydroxide or a zinc-bound water and in the protonation state of the essential His210 residue. Contacts of the catalytically important residues (Asp90, His210, Cys168, etc.) with the zinc center are characterized by the MD analyses. The nature of the Zn-OH(2) --> His210 proton transfer pathway connecting the two configurations was studied by means of QM calculations on cluster models while the relative stability of the two configurations was estimated from QM/MM calculations in the enzyme. From these results, a theoretical model for the kinetically active form of the B. cereus metalloenzyme is proposed. Some mechanistic implications and the influence of mutating the Cys168 residue are also discussed.