对于DUF512作为激素S-腺甲胺-巴胺结合域的结构证据
Bo Wang1, Amy E Solinski1, Matthew I Radle1
1Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
ACS bio & med chem Au
|December 23, 2024
概括
根基S-adenosylmethionine (SAM) 酶依赖于科巴胺 (Cbl) 使用Cbl进行甲基化. 这项研究确定DUF512是这些激进SAM酶中的新型Cbl结合域,揭示了细菌蛋白质中独特的结构特征.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 科巴胺 (Cbl) 依存的激素S-adenosylmethionine (SAM) 酶对于各种生物反应至关重要,主要是甲基化.
- 这些酶中的正规Cbl结合域通常具有N端的罗斯曼折叠.
- 甲基生成标记蛋白10 (Mmp10) 使用Cbl进行甲基化,但具有不同的C-终端Cbl结合域.
研究的目的:
- 研究未知功能的域512 (DUF512) 作为激进SAM酶中的新型Cbl结合域.
- 描述含有DUF512的蛋白质的结构和Cbl结合能力.
主要方法:
- 生物信息分析以确定激进SAM酶中的DUF512域.
- 过度表达和净化四种精选的含有DUF512的蛋白质.
- 用Cbl结合测试和X射线晶体学来确定蛋白质结构.
主要成果:
- 证实了四种含有DUF512的蛋白质可以结合Cbl.
- X射线晶体结构揭示了DUF512.2内部的Cbl结合域.
- 来自*Clostridium sporogenes*的结构是第一个具有PDZ域和前所未有的β3α4核心的激进SAM酶结构; *Pyrococcus furiosus*结构显示了一个不常见的 (βα) 5核心.
结论:
- 在激进的SAM酶中,DUF512代表了一种新型的Cbl结合域.
- 这些发现扩大了已知的Cbl-依赖的根基SAM酶的结构多样性,特别是在细菌中.
- 鉴定到的独特结构核心为这些酶的催化机制提供了新的见解.
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