A theoretical investigation of the functional role of the axial methionine ligand of the CU_A site in cytochrome c oxidase
A theoretical investigation of the functional role of the axial methionine ligand of the CU_A site in cytochrome c oxidase
复制标题
细胞色素c氧化酶中CU_A位点轴向蛋氨酸配体功能作用的理论研究
DOI：
10.1016/j.bbabio.2011.06.014
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Masaru Tateno
中科院分区：
文献类型：
--
作者：
Jiyoung Kang;Hiori Kino;Masaru Tateno
采用混合量子力学(QM)/分子力学（MM）计算方法研究了CuAsite氨基酸残基在牛细胞色素c氧化酶（CcO）中的功能作用。与先前使用缺乏轴向Met残基（即Cu2S2N2）的简化模型系统相比，涉及Cu dzxx轨道的分子轨道（MOs）的能级意外地增加。MO能量的提高源于反键轨道的形成，反键轨道是由Cu离子的dzx轨道与轴向配体的S和O原子的p轨道杂化而产生的。为了明确轴向Met配体的作用，计算了CuAsite的球内重组能，将Met残基分配到QM或MM区域。当将Met残基排除在QM区域外时，重组能略有增加。现有的实验数据和本研究的结构模型研究也表明，轴向Met残渣适度增加了CuAsite的氧化还原电位。因此，Met的作用可能是通过精细调制由两个Cys/His残基与Cu离子配位形成的CuA“平台”的电子结构来调节电子转移速率。这种调节将提供CuAsite的最佳氧化还原电位/重组能，从而促进CcO的后续协同反应，如质子泵和酶活性。这篇文章是题为“呼吸蛋白的变构协同”的特刊的一部分。
The functional roles of the amino acid residues of the CuAsite in bovine cytochrome c oxidase (CcO) were investigated by utilizing hybrid quantum mechanics (QM)/molecular mechanics (MM) calculations. The energy levels of the molecular orbitals (MOs) involving Cu dzxorbitals unexpectedly increased, as compared with those found previously with a simplified model system lacking the axial Met residue (i.e., Cu2S2N2). This elevation of MO energies stemmed from the formation of the anti-bonding orbitals, which are generated by hybridization between the dzxorbitals of Cu ions and the p-orbitals of the S and O atoms of the axial ligands. To clarify the roles of the axial Met ligand, the inner-sphere reorganization energies of the CuAsite were computed, with the Met residue assigned to either the QM or MM region. The reorganization energy slightly increased when the Met residue was excluded from the QM region. The existing experimental data and the present structural modeling study also suggested that the axial Met residue moderately increased the redox potential of the CuAsite. Thus, the role of the Met may be to regulate the electron transfer rate through the fine modulation of the electronic structure of the CuA“platform”, created by two Cys/His residues coordinated to the Cu ions. This regulation would provide the optimum redox potential/reorganization energy of the CuAsite, and thereby facilitate the subsequent cooperative reactions, such as the proton pump and the enzymatic activity, of CcO. This article is part of a Special Issue entitled: Allosteric cooperativity in respiratory proteins.