Interactions of bismuth complexes with metallothionein(II)
Interactions of bismuth complexes with metallothionein(II)
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DOI：
10.1074/jbc.274.41.29094
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发表时间：
1999-10-08
影响因子：
4.8
通讯作者：
Sadler, PJ
中科院分区：
文献类型：
--
作者：
Sun, HZ;Li, HY;Sadler, PJ
铋配合物被广泛用作抗溃疡药物，并能显著降低铂类抗癌药物的副作用。已知铋可诱导肾脏中金属硫蛋白（MT）的合成，但很少有关于铋配合物与金属硫蛋白相互作用的化学研究。在这里，我们发现Bi3+与金属硫蛋白结合强烈，化学计量比铋：MT = 7:1 (Bi7MT)，可以很容易地取代Zn2+和Cd2+。即使在强酸性溶液（pH值为1）中，铋仍然与蛋白质结合。柠檬酸铋与MT的反应比[Bi(EDTA)]（-）的反应快，且均表现为双相动力学。H-1核磁共振数据表明，Zn2+的位移速度快于Cd2+，并且Bi3+在NPT β -畴（三金属簇）中的位移速度比在α -畴（四金属簇）中的快得多。Bi7MT的扩展x射线吸收精细结构谱与谷胱甘肽和n -乙酰基- l-半胱氨酸配合物[Bi(GS)(3)]和[Bi(NAC)(3)]非常相似，其内配位球为3个硫原子，平均Bi- s距离为2.55埃，一些位点似乎含有额外的短Bi- o键2.2埃和长Bi- s键3.1埃，因此Bi7MT中的Bi3+位点与Zn2+和Cd2+相比具有高度畸变。
Bismuth complexes are widely used as anti-ulcer drugs and can significantly reduce the side effects of platinum anti-cancer drugs. Bismuth is known to induce the synthesis of metallothionein (MT) in the kidney, but there are few chemical studies on the interactions of bismuth complexes with metallothionein. Here we show that Bi3+ binds strongly to metallothionein with a stoichiometry bismuth:MT = 7:1 (Bi7MT) and can readily displace Zn2+ and Cd2+. Bismuth is still bound to the protein even in strongly acidic solutions (pH 1). Reactions of bismuth citrate with MT are faster than those of [Bi(EDTA)](-), and both exhibit biphasic kinetics. H-1 NMR data show that Zn2+ is displaced faster than Cd2+, and that both Zn2+ and Cd2+ in the beta-domain (three metal cluster) of NPT are displaced by Bi3+ much faster than from the alpha-domain (four metal cluster). The extended x-ray absorption fine structure spectrum of Bi7MT is very similar to that for the glutathione and N-acetyl-L-cysteine complexes [Bi(GS)(3)] and [Bi(NAC)(3)] with an inner coordination sphere of three sulfur atoms and average Bi-S distances of 2.55 Angstrom Some sites appear to contain additional short Bi-O bonds of 2.2 Angstrom and longer Bi-S bonds of 3.1 Angstrom The Bi3+ sites in Bi7MT are therefore highly distorted in comparison with those of Zn2+ and Cd2+.