拉索表酶MslH的结构揭示了金属依赖的酸催化机制
Yu Nakashima1, Atsushi Kawakami2, Yasushi Ogasawara3
1Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama, 930-0194, Japan.
Nature communications
|August 7, 2023
概括
拉索MS-271表酶MSLH使用离子和特定的氨基酸将L-型转化为D-型,这是RiPP生物合成的关键步骤.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 拉索是一种核糖体合成和翻译后修饰 (RiPPs).
- MS-271是一种由前体MslA衍生而来的拉索,在C端具有D-托.
- 酶MSLH催化MSLA的C端Trp21的表皮化,形成D-托,但其机制尚不清楚.
研究的目的:
- 阐明表酶MslH的催化机制,活性部位和辅因子.
- 了解RiPP生物合成中L-三酸转化为D-三酸的结构基础.
主要方法:
- MslH的X射线晶体学与MslA核心类型.
- 位点定向的突变发生.
- 进行对接模拟.
- 感应合等离子体质谱法 (ICP-MS).
主要成果:
- 确定MSLH是一种金属依赖性类表皮酶,具有类似氨酸的折叠.
- 该酶利用一个通过水分子协调的Ca (II) 离子.
- 两对His/Asp催化残留物通过酸化学促进可逆性表皮化.
结论:
- MslH采用了一种新的催化机制,涉及离子和特定的酸性/基性残留物.
- 这项研究揭示了RiPP生物合成中的关键表皮化步骤的结构和机制细节.
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