Thiolate ligands in metallothionein confer redox activity on zinc clusters
Thiolate ligands in metallothionein confer redox activity on zinc clusters
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DOI：
10.1073/pnas.95.7.3478
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发表时间：
1998-03-31
影响因子：
11.1
通讯作者：
Vallee, BL
中科院分区：
文献类型：
--
作者：
Maret, W;Vallee, BL
我们假设了一种新颖且通用的机制，其中半胱氨酸的氧化还原活性硫供体基团赋予蛋白质中稳定的锌位点氧化还原特性，因此，现在，较早的和随附的手稿[Maret，W，，Larsen，K.S，＆Vallee，B，L，（1997）FI uc。国家。阿卡德。科学，美国 94，2233-2237； Jiang, L.-J,, Maret, W. 和 Vallee, B, L, (1998) Proc。国家。阿卡德。科学，ASA 95，3483-3488；和 Jacob, C.、Maret, W 和 Vallee, B, L, (1998) Proc, Natl。阿卡德，科学。 USA 95, 3489-3494] 证明，金属硫蛋白 (MT) 簇中发现的具有多个锌/硫键的相互作用网络构成了一个配位单元，对于半胱氨酸配体的同时氧化和随后的锌释放至关重要。氧化还原试剂中 MT 的低位置 (< -366 mV) 允许其被相对温和的细胞氧化剂（特别是二硫化物）有效氧化，当 MT 暴露于过量的二硫代二吡啶，其所有 20 个半胱氨酸在 1 小时内被氧化，同时释放出所有 7 个锌原子；类似地，硫醇/二硫化物氧化还原酶 DsbA 与 MT 发生化学计量反应，释放锌，簇中的锌和硫配体处于似乎有利于二硫键形成的空间排列。联合起来，这篇手稿和上述手稿得出结论，细胞锌分布作为细胞能量状态的函数的控制是 MT 长期寻求的作用，这种特定的 MT 功能使人们普遍认为 MT 主要清除的观点变得可疑。自由基或解毒金属，并且与经常使用半胱氨酸作为蛋白质中的锌配体一致，分别作为硫醇和二硫化物的紧密和弱锌结合的手段。因此，我们将细胞还原能力的变化与MT中锌/硫网络的稳定性以及锌的相对流动性及其控制联系起来。
We postulate a novel and general mechanism in which the redox-active sulfur donor group of cyst(e)ine confers oxidoreductive characteristics an stable zinc sites in proteins, Thus, the present, an earlier, and accompanying manuscripts [Maret, W,, Larsen, K. S, & Vallee, B, L, (1997) FI uc. Natl. Acad. Sci, USA 94, 2233-2237; Jiang, L.-J,, Maret, W. & Vallee, B, L, (1998) Proc. Natl. Acad. Sci, ASA 95, 3483-3488; and Jacob, C., Maret, W, & Vallee, B, L, (1998) Proc, Natl. Acad, Sci. USA 95, 3489-3494] demonstrate that the interactive network featuring multiple zinc/sulfur bonds as found in the clusters of metallothionein (MT) constitutes a coordination unit critical for the concurrent oxidation of cysteine ligands and the ensuing release of zinc, The low position of MT (< -366 mV) on a scale of redox reagents allows its effective oxidation by relatively mild cellular oxidants, in particular disulfides, When MT is exposed to an excess of dithiodipyridine, all of its 20 cysteines are oxidized within 1 hr with the concomitant release of all 7 zinc atoms; similarly, the thiol/disulfide oxidoreductase DsbA reacts stoichiometrically with MT to release zinc, Zinc and sulfur ligands in the clusters are in a spatial arrangement that seemingly favors disulfide bond formation, Jointly, this and the above-mentioned manuscripts conclude that the control of cellular zinc distribution as a function of the energy state of the cell is the long sought role of MT, This specific MT function renders dubious the widely held belief that MT primarily scavenges radicals or detoxifies metals and is consistent with the frequent use of cysteine as a zinc ligand in proteins as a means of both tight and weak zinc binding of thiols and disulfides, respectively, Thus, we relate changes in the reducing power of the cell to the stability of the zinc/sulfur network in MT and the relative mobility of zinc and its control.