Water chain formation and possible proton pumping routes in Rhodobacter sphaeroides cytochrome c oxidase: a molecular dynamics comparison of the wild type and R481K mutant.
Water chain formation and possible proton pumping routes in Rhodobacter sphaeroides cytochrome c oxidase: a molecular dynamics comparison of the wild type and R481K mutant.
复制标题
球形红细菌细胞色素 c 氧化酶中的水链形成和可能的质子泵送路线：野生型和 R481K 突变体的分子动力学比较。
DOI：
10.1021/bi0502902
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发表时间：
2005
期刊：
影响因子：
2.9
通讯作者：
Cukier,RobertI
中科院分区：
文献类型：
--
作者：
Seibold,SteveA;Mills,DeniseA;Ferguson-Miller,Shelagh;Cukier,RobertI
细胞色素氧化酶（CcO）将来自氧化还原和氧化学的能量转化为支持质子易位并产生用于ATP生产的跨膜ΔμH+。分子动力学（MD）模拟探讨了能够参与质子易位的地层水链。注意力集中在血红素之间和以上的区域，在晶体学研究中没有确定明确的水链。精氨酸(R481) (Rhodobacter sphaeroidesnumbering),定位D-propionates之间的血红素,被突变体内赖氨酸和显示改变了活动符合质子电导的改变(钱、J。米尔斯,d . A。根据,L, Wang k . F。Hoganson, C·W。施密特,B。,他,C,巴布科克,g . T。达勒姆,B。,米勒特,F。,Ferguson-Miller,美国(2004年)角色的守恒的精氨酸对质子和电子转移在cytochromecoxidase Biochemistry43,5748−5756;（参见Mills等人的论文）。该突变体通过计算机构建，并将突变体与野生型的MD结果进行比较，探讨该突变体对氢键水链形成的影响。模拟结果表明，存在氢键水链，从E286穿过血红素上方的区域到达Mg2+，从E286到达血红素3d -丙酸和双核中心。R481K突变体不像野生型CcO那样形成那么多或那么广泛的水链，这是由于亚基I中螺旋III和IV之间的大环中残基的新构象，表明突变体中水链形成水平降低。这个环似乎在控制血红素上方氢键水链的形成中起作用。结果表明，质子运动的一种可能的门控机制包括环上的关键残基W172和Y175以及螺旋VI上的关键残基F282。
Cytochromecoxidase (CcO) converts the energy from redox and oxygen chemistry to support proton translocation and create a transmembrane ΔμH+used for ATP production. Molecular dynamics (MD) simulations were carried out to probe for the formation water chains capable of participating in proton translocation. Attention was focused on the region between and above theaanda3hemes where well-defined water chains have not been identified in crystallographic studies. An arginine (R481) (Rhodobacter sphaeroidesnumbering), positioned between the D-propionates of the hemes, had been mutated in vivo to lysine and showed to have altered activity consistent with an altered proton conductance [Qian, J., Mills, D. A., Geren, L., Wang, K. F., Hoganson, C. W., Schmidt, B., Hiser, C., Babcock, G. T., Durham, B., Millett, F., and Ferguson-Miller, S. (2004) Role of the conserved arginine pair in proton and electron transfer in cytochromecoxidase,Biochemistry43, 5748−5756; also see the accompanying paper by Mills et al.]. This mutant was created in silico, and the MD results for the mutant and wild type were compared to explore the effects on the formation of hydrogen-bonded water chains by this mutation. The simulations reveal the presence of hydrogen-bonded water chains that lead from E286 through the region above the hemes to the Mg2+, and from E286 to the hemea3D-propionate and the binuclear center. The R481K mutant does not form as many, or as extensive, water chains as wild-type CcO, due to a new conformation of residues in a large loop between helices III and IV in subunit I, indicating a reduction in the level of water chain formation in the mutant. This loop appears to play a role in controlling the formation of hydrogen-bonded water chains above the hemes. The results suggest a possible gating mechanism for proton movement that includes key residues W172 and Y175 on the loop and F282 on helix VI.