Bacillus subtilis arsenate reductase is structurally and functionally similar to low molecular weight protein tyrosine phosphatases
Bacillus subtilis arsenate reductase is structurally and functionally similar to low molecular weight protein tyrosine phosphatases
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DOI：
10.1073/pnas.241397198
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发表时间：
2001-11-20
影响因子：
11.1
通讯作者：
Su, XD
中科院分区：
文献类型：
--
作者：
Bennett, MS;Guan, Z;Su, XD
砷酸盐是一种丰富的氧阴离子，由于它能够模仿磷酸基团，因此对细胞有毒。砷酸还原酶（EC 1.97.1.5；由细菌中的 arsC 基因编码）通过将砷酸还原为亚砷酸盐，参与原核生物和酵母中实现砷酸抗性；然后亚砷酸盐由特定的运输商出口。还原形式的枯草芽孢杆菌砷酸还原酶的晶体结构在其活性位点结合有硫酸根离子，分辨率为 1.6 埃。尽管序列同一性非常低，但砷酸还原酶和牛低分子量蛋白酪氨酸磷酸酶之间存在显着的结构相似性。它们的活性位点之间的相似性特别高。通过在体外显示砷酸还原酶的磷酸酶活性，进一步证实了这种结构同源性在功能上是相关的。因此，我们可以根据低分子量蛋白酪氨酸磷酸酶机制来理解砷酸还原，并解释Cys-10、Cys-82、Cys-89、Arg-16和Asp-105等必需残基的催化作用。提出了“三重半胱氨酸氧化还原中继”用于砷酸盐还原机制。
Arsenate is an abundant oxyanion that, because of its ability to mimic the phosphate group, is toxic to cells. Arsenate reductase(EC 1.97.1.5; encoded by the arsC gene in bacteria) participates to achieve arsenate resistance in both prokaryotes and yeast by reducing arsenate to arsenite; the arsenite is then exported by a specific transporter. The crystal structure of Bacillus subtilis arsenate reductase in the reduced form with a bound sulfate ion in its active site is solved at 1.6-Angstrom resolution. Significant structural similarity is seen between arsenate reductase and bovine low molecular weight protein tyrosine phosphatase, despite very low sequence identity. The similarity is especially high between their active sites. It is further confirmed that this structural homology is relevant functionally by showing the phosphatase activity of the arsenate reductase in vitro. Thus, we can understand the arsenate reduction in the light of low molecular weight protein tyrosine phosphatase mechanism and also explain the catalytic roles of essential residues such as Cys-10, Cys-82, Cys-89, Arg-16, and Asp-105. A "triple cysteine redox relay" is proposed for the arsenate reduction mechanism.