Structural Characterization and Ligand-Induced Conformational Changes of SenB, a Se-Glycosyltransferase Involved in Selenoneine Biosynthesis.
Structural Characterization and Ligand-Induced Conformational Changes of SenB, a Se-Glycosyltransferase Involved in Selenoneine Biosynthesis.
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DOI：
10.1021/acs.biochem.3c00452
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发表时间：
2023-12-05
期刊：
影响因子：
2.9
通讯作者：
Davis, Katherine M.
中科院分区：
文献类型：
--
作者：
Ireland, Kendra A.;Kayrouz, Chase M.;Huang, Jonathan;Seyedsayamdost, Mohammad R.;Davis, Katherine M.
硒 (Se) 是一种必需的微量营养素，天然存在于蛋白质、核酸和天然产物中。与硒蛋白和硒核酸不同，人们对将硒掺入小分子的生物合成酶的结构知之甚少。在这里，我们报道了 SenB 的 X 射线晶体结构，SenB 是第一个已知的 Se-糖基转移酶，最近发现它参与含硒代谢物硒酮的生物合成。 SenB 使用硒磷酸盐和活化的尿苷二磷酸糖分别作为 Se 和糖基供体来催化 C-Se 键形成，使其成为第一个已知的硒糖合酶，也是迄今为止发现的仅有的四种真正的 C-Se 键形成酶之一。我们的晶体结构确定为 2.25 Å 分辨率，表明 SenB 是一种 B 型糖基转移酶，显示出具有两个球状 Rossmann 样结构域和一个催化结构域间裂缝的典型折叠。通过采用互补的结构生物学技术，我们发现 SenB 经历了局部和整体底物诱导的构象变化，表现出 α 螺旋性的显着增加以及向更紧凑构象的转变。我们的结果提供了 SenB 的第一个结构，并为未来进一步的生化表征奠定了基础。
Selenium (Se) is an essential micronutrient that is found naturally in proteins, nucleic acids, and natural products. Unlike selenoproteins and selenonucleic acids, little is known about the structures of biosynthetic enzymes that incorporate Se into small molecules. Here, we report the X-ray crystal structure of SenB, the first known Se-glycosyltransferase that was recently found to be involved in the biosynthesis of the Se-containing metabolite selenoneine. SenB catalyzes C–Se bond formation using selenophosphate and an activated uridine diphosphate sugar as a Se and glycosyl donor, respectively, making it the first known selenosugar synthase and one of only four bona fide C–Se bond-forming enzymes discovered to date. Our crystal structure, determined to 2.25 Å resolution, reveals that SenB is a type B glycosyltransferase, displaying the prototypical fold with two globular Rossmann-like domains and a catalytic interdomain cleft. By employing complementary structural biology techniques, we find that SenB undergoes both local and global substrate-induced conformational changes, demonstrating a significant increase in α-helicity and a transition to a more compact conformation. Our results provide the first structure of SenB and set the stage for further biochemical characterization in the future.
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