对RufO的结构和光谱表征表明,它在鲁福米辛生物合成中发挥了新的生物学作用
Stephanie Jordan1, Bingnan Li1, Ephrahime Traore2
1Department of Chemistry, University of Georgia, Athens, Georgia, USA.
The Journal of biological chemistry
|July 14, 2023
概括
研究人员研究了RufO,一种类似细胞染色体P450的酶,以及它在合成3 - 铁氨酸用于鲁福米辛抗生素中的作用. 结果表明,氨酸不是RufO的基质,表明化发生在组合后.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 药物发现 药物发现 药物发现
背景情况:
- 鲁福米辛是来自actinomycetes的循环七环,具有针对*Mycobacterium结核病*的潜力.
- 这些酸含有非蛋白质原性氨基酸,包括3 - - 铁.
- 假设RufO是一种类似于P450细胞染色体的酶,可以使用O2和NO制造3-酸铁氨酸.
研究的目的:
- 为了研究RufO的生物功能.
- 为了确定铁是否是RufO介导化的基质.
- 了解鲁福米辛及其独特成分的生物合成.
主要方法:
- 谱学方法来监测血红细胞中心的变化.
- 鲁福的X射线晶体学 (1.89-Å分辨率)
- 分子对接模拟. 分子对接模拟.
主要成果:
- 在连接体相互作用时没有观察到低旋转到高旋转状态的过渡或显著的氧化还原电位转移.
- 鲁福晶体结构显示出一个灵活的,开放的活性部位,在很大程度上暴露于溶剂.
- 酶的远端口袋是宽和疏水的,不适合稳定自由氨基酸.
- 分子对接建议了替代基质的可能性.
结论:
- 实验和计算数据不支持铁素作为RufO的基质.
- 3-铁的形成可能发生在组装后.
- 在非核糖体生物合成中,RufO可能具有新的功能.
- 这项研究提供了关于合成中独特的化机制的见解.
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