Reaction of Thiosulfate Dehydrogenase with a Substrate Mimic Induces Dissociation of the Cysteine Heme Ligand Giving Insights into the Mechanism of Oxidative Catalysis.
Reaction of Thiosulfate Dehydrogenase with a Substrate Mimic Induces Dissociation of the Cysteine Heme Ligand Giving Insights into the Mechanism of Oxidative Catalysis.
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DOI：
10.1021/jacs.2c06062
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发表时间：
2022-10-12
影响因子：
15
通讯作者：
Butt, Julea N.
中科院分区：
文献类型：
--
作者：
Jenner, Leon P.;Crack, Jason C.;Kurth, Julia M.;Soldanova, Zuzana;Brandt, Linda;Sokol, Katarzyna P.;Reisner, Erwin;Bradley, Justin M.;Dahl, Christiane;Cheesman, Myles R.;Butt, Julea N.
硫代硫酸盐脱氢酶是细菌的细胞色素，有助于无机硫的氧化。这些酶的活性位点含有低自旋c型血红素，具有Cys - /His轴向连接。然而，这些血红素的还原电位比硫代硫酸盐/四硫代酸对（Em, +198 mV）的还原电位要负几百mV，这使得硫代硫酸盐的氧化能力难以合理化。本文描述了空肠弯曲杆菌硫代硫酸盐脱氢酶（TsdA）与硫代硫酸盐类似物亚硫酸盐的反应。该反应导致活性位点Cys在化学计量上转化为半胱氨酸磺酸盐（Cα-CH2-S-SO3 -），使得该蛋白以一种非常类似于硫代硫酸盐氧化途径中携带半胱氨酸硫代硫酸盐（Cα-CH2-S-SSO3 -）的中间体的形式存在。稳定磺化蛋白的活性位点血红素显示出比Cys - / his -连接状态高约200 mV的电位。这可以解释酶的硫代硫酸盐氧化活性，并允许我们提出硫代硫酸盐氧化的催化机制。底物驱动的Cys血红素配体释放允许侧链提供底物结合和氧化还原转化的位点；然后邻近的血红素简单地为电子传递到合适的伙伴提供一个位点。这种化学反应不同于在气敏血红蛋白和细胞色素P450等酶中发现的胱氨酸连接血红素所显示的化学反应。因此，进一步的一类硫代酸连接血红素被提出，例如TsdA中心已经进化到催化硫的无机氧阴离子的受控氧化还原转化。
Thiosulfate dehydrogenases are bacterial cytochromes that contribute to the oxidation of inorganic sulfur. The active sites of these enzymes contain low-spin c-type heme with Cys–/His axial ligation. However, the reduction potentials of these hemes are several hundred mV more negative than that of the thiosulfate/tetrathionate couple (Em, +198 mV), making it difficult to rationalize the thiosulfate oxidizing capability. Here, we describe the reaction of Campylobacter jejuni thiosulfate dehydrogenase (TsdA) with sulfite, an analogue of thiosulfate. The reaction leads to stoichiometric conversion of the active site Cys to cysteinyl sulfonate (Cα-CH2-S-SO3–) such that the protein exists in a form closely resembling a proposed intermediate in the pathway for thiosulfate oxidation that carries a cysteinyl thiosulfate (Cα-CH2-S-SSO3–). The active site heme in the stable sulfonated protein displays an Em approximately 200 mV more positive than the Cys–/His-ligated state. This can explain the thiosulfate oxidizing activity of the enzyme and allows us to propose a catalytic mechanism for thiosulfate oxidation. Substrate-driven release of the Cys heme ligand allows that side chain to provide the site of substrate binding and redox transformation; the neighboring heme then simply provides a site for electron relay to an appropriate partner. This chemistry is distinct from that displayed by the Cys-ligated hemes found in gas-sensing hemoproteins and in enzymes such as the cytochromes P450. Thus, a further class of thiolate-ligated hemes is proposed, as exemplified by the TsdA centers that have evolved to catalyze the controlled redox transformations of inorganic oxo anions of sulfur.
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