Determinants of the relative reduction potentials of type-1 copper sites in proteins
Determinants of the relative reduction potentials of type-1 copper sites in proteins
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DOI：
10.1021/ja049345y
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发表时间：
2004-06-30
影响因子：
15
通讯作者：
Jensen, JH
中科院分区：
文献类型：
--
作者：
Li, H;Webb, SP;Jensen, JH
通过量子力学计算，研究了还原电位范围从 260 mV 到超过 1000 mV 的 6 个 1 型铜位点（黄瓜星花素、铜绿假单胞菌天青蛋白、杨树质体蓝素、灰葡萄球菌漆酶、氧化亚铁黄素和人铜蓝蛋白）的相对 Cu2+/Cu+ 还原电位。与实验值相比，还原电位的范围和相对顺序得到了很好的再现。研究表明，蓝铜位点相对还原电位的主要结构决定因素位于铜原子的 6 埃范围内。进一步分析表明，1 型铜位点的还原电位差异是由轴向配体相互作用、与 S-Cys 的氢键结合以及蛋白质对内球配体方向的限制引起的。黄瓜星花青蛋白的低还原电位主要是由于轴向位置的谷氨酰胺配体，而不是像其他蛋白质那样的蛋氨酸或疏水残基。与杨树质体蓝蛋白相比，与主链羰基基团更强的相互作用是导致铜绿假单胞菌天青蛋白还原电位较低的主要原因，而对于 C. cinereus 漆酶和 T. 氧化亚铁黄素蓝蛋白来说，情况正好相反。轴向甲硫氨酸配体的缺乏也显着促进了灰葡萄球菌漆酶和人铜蓝蛋白的还原潜力的增加。然而，就 C. cinereus 漆酶而言，这种增加会因 S-Cys 上仅存在一个酰胺 NH 氢键（而不是其他蛋白质中的两个）而减弱。在人铜蓝蛋白中，赤道配体方向的结构扭曲进一步增加了还原电位。
The relative Cu2+/Cu+ reduction potentials of six type-1 copper sites (cucumber stellacyanin, P. aeruginosa azurin, poplar plastocyanin, C. cinereus laccase, T. ferrooxidans rusticyanin, and human ceruloplasmin), which lie in a reduction potential range from 260 mV to over 1000 mV, have been studied by quantum mechanical calculations. The range and relative orderings of the reduction potentials are reproduced very well compared to experimental values. The study suggests that the main structural determinants of the relative reduction potentials of the blue copper sites are located within 6 Angstrom of the Cu atoms. Further analysis suggests that the reduction potential differences of type-1 copper sites are caused by axial ligand interactions, hydrogen bonding to the S-Cys, and protein constraint on the inner sphere ligand orientations. The low reduction potential of cucumber stellacyanin is due mainly to a glutamine ligand at the axial position, rather than a methionine or a hydrophobic residue as in the other proteins. A stronger interaction with a backbone carbonyl group is a prime contributor to the lower reduction potential of P. aeruginosa azurin as compared to poplar plastocyanin, whereas the reverse is true for C. cinereus laccase and T. ferrooxidans rusticyanin. The lack of an axial methonine ligand also contributes significantly to the increased reduction potentials of C. cinereus laccase and human ceruloplasmin. However, in the case of C. cinereus laccase, this increase is attenuated by the presence of only one amide NH hydrogen bond to the S-Cys rather than two in the other proteins. In human ceruloplasmin the reduction potential is further increased by the structural distortion of the equatorial ligand orientation.