在一个新的多核RiPP自然产品中安装单个和循环 ω-宏循环的双重功能ATP抓取联酶的结构基础
Gengxiang Zhao1, Dalibor Kosek2, Hong-Bing Liu1
1Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, United States.
Journal of the American Chemical Society
|May 24, 2021
概括
研究人员特征了化,一种新型的多核核核合成和翻译后修饰 (RiPP). 这项研究揭示了RiPP生物合成中通过ATP- 接联酶CdnC形成 ω- 的结构基础.
科学领域:
- 生物化学
- 结构生物学
- 自然产品化学
背景情况:
- 核糖体合成和翻译后修饰的 (RiPPs) 包括,其特征是由ATP-链酶形成的宏环和胺.
- 现有的草类如微维里丁,图灵丁和乐素表现出多样化的宏循环模式,包括带有的三环核和带有 ω-键的发针拓.
研究的目的:
- 描述菌,一种来自菌的新型多核RiPP.
- 在RiPP生物合成中通过ATP-抓取连接酶阐明 ω-键的结构基础.
主要方法:
- 在2.44 Å分辨率下与ADP,领导和基质复合的ATP-抓取C的晶体结构确定.
- 高分辨率质谱 (HRMS/MS) 用于化的分析.
- 使用系统变化的序进行体外酶活性测定.
主要成果:
- 克里索维里丁包括四个连续的五或六个残留的宏循环,其核心类似于微维里丁.
- 在基质结合时,晶体结构显示了CdnC酶的显著构造变化.
- 一个对接的ATP模型表明γ-酸盐与Asp受体残留的接近,支持N-到C终端宏循环.
结论:
- 这项研究为了解RiPPs中的 ω-键形成提供了结构基础.
- 已识别的两个或三个氨基酸的模板元素是对酶活性至关重要的.
- 这些发现有助于进一步了解草酸生物合成和ATP- 草链酶的功能.
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