在金属生物合成过程中通过金属控制稳脱酶活性
Christine Hajjar1, Roberto Fanelli2, Clémentine Laffont1
1Aix Marseille Université , CEA, CNRS, BIAM, F-13108 Saint Paul-Lez-Durance , France.
Journal of the American Chemical Society
|March 23, 2019
概括
黄金葡萄球菌CntM酶产生葡萄球菌金属. 和铜等金属离子可以激活或抑制CntM活动,这表明一种新的金属吸收调节机制.
科学领域:
- 生物化学
- 微生物学
- 结构生物学
背景情况:
- 酶调节对于适应环境变化至关重要,特别是对于金属依赖的金属吸收.
- 黄金葡萄球菌利用广谱金属来获取金属,需要精确调节其产量.
研究的目的:
- 通过化学合成中间体xNA来表征CntM酶.
- 阐明CntM的结构和功能,该酶负责稳固素生物合成的最后一步.
- 研究各种金属离子对CntM活动的影响.
主要方法:
- 化学合成的xNA中间体.
- 用X射线结晶学来确定CntM在不同状态下的三维结构 (apo,基质结合,产品结合).
- 用不同度的不同金属离子 (Zn2+,Cu2+,Mn2+,Co2+,Ni2+) 进行酶活性测定.
主要成果:
- 对xNA的化学合成是成功的,证实了CntM的蛋白合成活性.
- CntM的晶体结构显示出一个"开放"的构造,xNA基质通过Tyr240的π-π相互作用得到稳定.
- 金属离子表现出复杂的调节作用: Zn2+ 和 Cu2+ 是低度的激活剂,高度的抑制剂,Mn2+ 是一致的激活剂,而 Co2+ 和 Ni2+ 是抑制剂.
结论:
- 提出了一个模型,其中对xNA的金属离子亲和和CntM上的抑制位点决定了激活或抑制,调节了金属孔的产生.
- 这种依赖于金属的CntM调节可能发生在体内,基于细胞内金属水平的微调金属产量.
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