由依赖α-基酸盐的单核非血铁酶形成内氧化物
Wupeng Yan1, Heng Song2, Fuhang Song3
1Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA.
Nature
|November 3, 2015
概括
研究人员发现了由Aspergillus fumigatus fumitremorgin B内氧化酶 (FtmOx1) 形成内氧化物的新机制. 一个关键的氨酸残留物屏蔽了活性部位,将催化转向内氧化物合成而不是化.
科学领域:
- 生物化学
- 酵素学
- 结构生物学
背景情况:
- 含有过氧的二次代谢产物对健康有好处,但它们的生物合成机制尚不清楚.
- 前列腺素H合成酶是唯一一个具有良好特征的内氧化物生物合成酶,利用血辅因子.
- 来自Aspergillus fumigatus的Fumitremorgin B内氧化酶 (FtmOx1) 是一种新型的依赖α- 基酸盐的单核非血铁酶,可催化内氧化物形成.
研究的目的:
- 通过FtmOx1阐明内氧化物形成的机制细节.
- 调查特定的氨酸残留物 (Y224) 在FtmOx1催化中的作用.
- 描述参与酶反应的短暂基物种.
主要方法:
- 对FtmOx1及其二元复合物的X射线结晶学与α-甲酸盐和fumitremorgin B.
- Y224残留物的位点定向突变发生.
- 停止的光学吸收光谱.
- 结灭电子磁共振 (EPR) 光谱
主要成果:
- 晶体结构揭示了α-酸与铁中心的结合,而Y224则屏蔽了氧激活部位.
- 将Y224转化为氨酸或氨酸将催化从内氧化物形成转化为氧化.
- 在FtmOx1催化过程中,光谱分析提供了短暂基物种的证据.
结论:
- FtmOx1采用一种独特的内氧化物形成机制,与已知的含血酶不同.
- Y224残留在基质选择性和指导反应途径方面发挥着关键作用.
- 这项研究揭示了一种新型的酶途径,涉及内氧化物生物合成的中间激素.
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