Crystal structure analysis of human Sirt2 and its ADP-ribose complex
Crystal structure analysis of human Sirt2 and its ADP-ribose complex
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DOI：
10.1016/j.jsb.2013.02.012
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发表时间：
2013-05-01
影响因子：
3
通讯作者：
Steegborn, Clemens
中科院分区：
文献类型：
--
作者：
Moniot, Sebastien;Schutkowski, Mike;Steegborn, Clemens
Sirtuins 是 NAD(+) 依赖性蛋白脱乙酰酶，可调节新陈代谢和衰老相关过程。 Sirt2 是七种哺乳动物 Sirtuins (Sirt1-7) 中唯一的细胞质亚型，有关该亚型的结构信息有限。我们将 Sirt2 与产品类似物 ADPribose 形成复合物进行结晶，并以 2.3 埃的分辨率解析了 Sirt2 配体复合物的第一个晶体结构。此外，我们重新精炼了 Sirt2 apoform 的结构，并分析了与配体结合相关的构象变化，以深入了解该酶的动力学。我们的分析还提供了有关 Sirt2 肽底物结合和 Sirt2 特异性蛋白质区域的结构状态的信息，我们的见解和新型 Sirt2 晶型为开发 Sirt2 特异性抑制剂提供了有用的工具。 (c) 2013 Elsevier Inc. 保留所有权利。
Sirtuins are NAD(+)-dependent protein deacetylases that regulate metabolism and aging-related processes. Sirt2 is the only cytoplasmic isoform among the seven mamalian Sirtuins (Sirt1-7) and structural information concerning this isoform is limited. We crystallized Sirt2 in complex with a product analog, ADPribose, and solved this first crystal structure of a Sirt2 ligand complex at 2.3 angstrom resolution. Additionally, we re-refined the structure of the Sirt2 apoform and analyzed the conformational changes associated with ligand binding to derive insights into the dynamics of the enzyme. Our analyses also provide information on Sirt2 peptide substrate binding and structural states of a Sirt2-specific protein region, and our insights and the novel Sirt2 crystal form provide helpful tools for the development of Sirt2 specific inhibitors. (c) 2013 Elsevier Inc. All rights reserved.