Relating the Diffusion of Small Ligands in Human Neuroglobin to Its Structural and Mechanical Properties
Relating the Diffusion of Small Ligands in Human Neuroglobin to Its Structural and Mechanical Properties
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DOI：
10.1021/jp906854x
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发表时间：
2009-12-17
影响因子：
3.3
通讯作者：
Sacquin-Mora, Sophie
中科院分区：
文献类型：
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作者：
Bocahut, Anthony;Bernad, Sophie;Sacquin-Mora, Sophie
神经红蛋白（Neuroglobin, Ngb）是最近发现的一种球蛋白家族成员，它在缺氧时在脑组织中过度表达。与更经典的球蛋白（如肌红蛋白和血红蛋白）不同，它的特点是六配位血红素，尽管近年来进行了大量研究，但它的生理作用仍然未知。人类Ngb的另一个重要特征是存在两个半胱氨酸残基（Cys46和Cys55），已知它们形成分子内二硫桥。由于前人在人类Ngb上的研究报道了其配体结合特性可以由Fe2+原子（血红素部分）的配位状态和巯基的氧化还原状态控制，因此我们选择开发一种结合粗粒布朗动力学和全原子分子动力学和元动力学的模拟方法。我们研究了小配体（CO， NO和O-2）在人类Ngb不同状态的珠蛋白内腔网络中的扩散。我们的研究结果表明，蛋白质的结构和力学性能与配体迁移途径有关，当改变硫醇的氧化还原态和铁的配位态时，配体迁移途径可以被广泛地改变。我们认为配体结合有利于具有内部二硫桥的五配位物种。
Neuroglobin (Ngb), a recently discovered member of the globin family, is overexpressed in the brain tissues over oxygen deprivation. Unlike more classical globins, such as myoglobin and hemoglobin, it is characterized by a hexacoordinated heme, and its physiological role is still unknown, despite the numerous investigations made oil the protein in recent years. Another important specific feature of human Ngb is the presence of two cysteine residues (Cys46 and Cys55), which are known to form an intramolecular disulfide bridge. Since previous work on human Ngb reported that its ligand binding properties could be controlled by the coordination state of the Fe2+ atom (in the heme moiety) and the redox state of the thiol groups, we choose to develop a Simulation approach combining coarse-grain Brownian dynamics and all-atom Molecular dynamics and metadynamics. We have Studied the diffusion of small ligands (CO, NO, and O-2) in the globin internal cavity network for Various states of human Ngb. Our results show how the structural and mechanical properties of the protein can be related to the ligand migration pathway, which can be extensively modified when changing the thiol's redox state and the iron's coordination state. We suggest that ligand binding is favored in the pentacoordinated species bearing an internal disulfide bridge.