Biochemical discrimination between selenium and sulfur 1: a single residue provides selenium specificity to human selenocysteine lyase.
Biochemical discrimination between selenium and sulfur 1: a single residue provides selenium specificity to human selenocysteine lyase.
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DOI：
10.1371/journal.pone.0030581
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Högbom M
中科院分区：
文献类型：
--
作者：
Collins R;Johansson AL;Karlberg T;Markova N;van den Berg S;Olesen K;Hammarström M;Flores A;Schüler H;Schiavone LH;Brzezinski P;Arnér ES;Högbom M
硒和硫是两种密切相关的基本元素，在自然界中用于大量的生化反应。虽然硒在较高浓度下有毒，但它是一种必需的微量元素，以硒代半胱氨酸 (Sec) 的形式掺入硒蛋白中，硒代半胱氨酸是半胱氨酸 (Cys) 的硒类似物。 Sec 裂合酶 (SCL) 和 Cys 脱硫酶 (CD) 催化从 Sec 或 Cys 中去除硒或硫，并且通常作用于两种底物。相比之下，人类 SCL (hSCL) 对 Sec 具有特异性，尽管 Sec 和 Cys 之间的唯一区别在于单个原子的身份。这种硒与硫区别的化学基础尚不清楚。在这里，我们描述了 hSCL 的 X 射线晶体结构，并将 Asp146 确定为提供 Sec 特异性的关键残基。 D146K 变异导致 Sec 特异性丧失和 CD 活性出现。动态活性位点片段还为 Sec 裂解产生的硒化物的直接产物传递提供了结构先决条件，从而避免了活性硒化物物质释放到细胞中。因此，我们在这里定义了一个分子决定因素，用于区分单个硒与硫原子（具有非常相似的化学性质的元素）之间的酶特异性。因此，我们的研究结果为人类硒和硒蛋白周转和代谢的关键控制水平提供了分子见解。
Selenium and sulfur are two closely related basic elements utilized in nature for a vast array of biochemical reactions. While toxic at higher concentrations, selenium is an essential trace element incorporated into selenoproteins as selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys and generally act on both substrates. In contrast, human SCL (hSCL) is specific for Sec although the only difference between Sec and Cys is the identity of a single atom. The chemical basis of this selenium-over-sulfur discrimination is not understood. Here we describe the X-ray crystal structure of hSCL and identify Asp146 as the key residue that provides the Sec specificity. A D146K variant resulted in loss of Sec specificity and appearance of CD activity. A dynamic active site segment also provides the structural prerequisites for direct product delivery of selenide produced by Sec cleavage, thus avoiding release of reactive selenide species into the cell. We thus here define a molecular determinant for enzymatic specificity discrimination between a single selenium versus sulfur atom, elements with very similar chemical properties. Our findings thus provide molecular insights into a key level of control in human selenium and selenoprotein turnover and metabolism.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Mihara, H;Kurihara, T;Esaki, N
通讯作者：
Esaki, N
影响因子：
56.9
作者：
Kryukov, GV;Castellano, S;Gladyshev, VN
通讯作者：
Gladyshev, VN
影响因子：
2.7
作者：
Mihara, H;Kurihara, T;Esaki, N
通讯作者：
Esaki, N
影响因子：
4.8
作者：
Mihara, H;Kurihara, T;Esaki, N
通讯作者：
Esaki, N