NMR structure of oxidized glutaredoxin 3 from Escherichia coli
NMR structure of oxidized glutaredoxin 3 from Escherichia coli
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DOI：
10.1006/jmbi.2000.4145
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发表时间：
2000-10-27
影响因子：
5.6
通讯作者：
Berndt, KD
中科院分区：
文献类型：
--
作者：
Nordstrand, K;Sandström, A;Berndt, KD
测定了大肠杆菌氧化型谷氧还蛋白3 [C65 Y]的高精度NMR结构。包括二硫桥在内的活性位点的构象与猪肝和T4噬菌体中的谷氧还蛋白的构象高度相似。与先前确定的结构的谷氧还蛋白3 [C14 S，C65 Y]与谷胱甘肽复合物的比较揭示了自由和底物结合形式之间的构象变化，其中包括保守的活性位点酪氨酸残基的侧链。在氧化形式中，这种酪氨酸是溶剂暴露的，而在与谷胱甘肽的混合二硫化物中，它采用较少暴露的构象，通过氢键稳定。这些结构进一步表明，谷胱甘肽和谷氧还蛋白3之间形成共价键是必需的，以便在谷胱甘肽肽结合后诱导这些结构变化。这可以解释所观察到的低亲和力的谷氧还蛋白的S-封闭的谷胱甘肽类似物，尽管事实上，谷氧还蛋白是谷胱甘肽混合二硫化物的高度特异性还原剂。(C)北京大学出版社.
A high precision NMR structure of oxidized glutaredoxin 3 [C65Y] from Escherichia coli has been determined. The conformation of the active site including the disulphide bridge is highly similar to those in glutaredoxins from pig liver and T4 phage. A comparison with the previously determined structure of glutaredoxin 3 [C14S, C65Y] in a complex with glutathione reveals conformational changes between the free and substrate-bound form which includes the sidechain of the conserved, active site tyrosine residue. In the oxidized form this tyrosine is solvent exposed, while it adopts less exposed conformation, stabilized by hydrogen bonds, in the mixed disulfide with glutathione. The structures further suggest that the formation of a covalent linkage between glutathione and glutaredoxin 3 is necessary in order to induce these structural changes upon binding of the glutathione peptide. This could explain the observed low affinity of glutaredoxins for S-blocked glutathione analogues, in spite of the fact that glutaredoxins are highly specific reductants of glutathione mixed disulfides. (C) 2000 Academic Press.