Laboratoire de Biochimie Théorique, UPR 9080 CNRS Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France.
J Phys Chem B. 2009 Dec 17;113(50):16257-67. doi: 10.1021/jp906854x.
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 on 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 Fe(2+) 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.
神经球蛋白（Ngb）是球蛋白家族中最近发现的成员，在缺氧的脑组织中过度表达。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，尽管近年来对该蛋白进行了大量研究，但它的生理作用仍不清楚。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），已知这两个残基形成一个分子内二硫键。由于以前关于人 Ngb 的研究报告称，其配体结合特性可以通过血红素部分的 Fe(2+)原子（在配位状态）和巯基的氧化还原状态来控制，因此我们选择开发一种结合粗粒度布朗动力学和全原子分子动力学和元动力学的模拟方法。我们研究了小分子配体（CO、NO 和 O(2)) 在人 Ngb 的各种状态下在球蛋白内部腔网络中的扩散。我们的结果表明，蛋白质的结构和力学性质如何与配体迁移途径相关，当改变硫醇的氧化还原状态和铁的配位状态时，配体迁移途径可以得到广泛的修饰。我们建议，在具有内部二硫键的五配位物种中，配体结合更有利。
