ClbS 是一种循环基酶,使其对可利巴克产生抗性
Prabhanshu Tripathi1, Emilee E Shine2,3, Alan R Healy3,4
1Department of Chemistry, University of Florida , Gainesville, Florida 32611, United States.
Journal of the American Chemical Society
|November 8, 2017
概括
通过分解它们的环,ClbS酶保护细菌免受毒性大肠杆菌的侵害. 这一发现揭示了对细菌生存和预防自我诱导的基因毒性至关重要的新型环酶机制.
科学领域:
- 微生物学
- 分子生物学
- 生物化学
背景情况:
- 大肠杆菌具有clb基因集群,产生转化为基因毒性大肠杆菌的前大肠杆菌.
- 科利巴克丁与结直肠癌的发展有关,但几种 clb 基因产物的功能尚不清楚.
- 细菌对 colibactin 毒性的耐药性机制尚未完全理解.
研究的目的:
- 为了阐明ClbS的分子功能和结构,这是一种参与 colibactin耐药性的蛋白质.
- 了解ClbS如何在 colibactins 的存在下促进细菌活力.
主要方法:
- 确定了ClbS的2.1 Å的X射线结构.
- 使用合成 colibactin 模拟物和 ClbS 进行了体外生化测试.
- 使用ClbS的活性位子突变来检测其酶活性.
主要成果:
- ClbS结构揭示了潜在的 colibactin 结合位点和与水溶酶的相似性.
- ClbS表现出环酶的活性,将胆固醇的基因毒性环酶转化为无害的产物.
- 使用合成 colibactin 模拟物和活性位子突变物证实了这种酶活性.
结论:
- 通过打开必需的环氧环,ClbS作为环氧基酶,通过打开必需的环氧环来排毒大肠杆菌.
- 这种酶在保护细菌免受自我诱导的基因毒性方面发挥着至关重要的作用,确保细菌的生存能力.
- 这项研究提供了对细菌环氨酸和其在抗 colibactin 的作用的第一个分子见解.
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