循环进化模式塑造了Trichothecenes的TRI101/201的催化效率:对蛋白质基质相互作用的洞察
Zezheng Yang1, Nana Zhou2, Xukai Jiang3
1Taishan College, Shandong University, 266237 Qingdao, China.
Journal of chemical information and modeling
|October 11, 2023
概括
通过乙化,TRI101/201酶通过乙化来排毒有毒的三甲. 一个无序的循环控制了结合的稳定性,解释了对脱氧尼瓦伦醇和T-2毒素的差异性酶活性.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 菌类毒理学 菌类毒理学
背景情况:
- 三甲是一种由类真菌产生的有毒真菌毒素.
- 通过乙化,TRI101/201酶对于三甲脱毒至关重要.
- 之前的研究表明,TRI101/201酶具有明显的基质特异性和动力特性.
研究的目的:
- 调查TRI101/201酶对各种三甲的不同催化活性背后的机制.
- 阐明结构特征,特别是内在无序循环在酶基质结合和催化效率中的作用.
主要方法:
- 结构生物信息学分析.
- 分子动力学模拟.分子动力学模拟.
- 分析蛋白质 - 配体结合相互作用和稳定性.
主要成果:
- 酶基质结合的稳定性是由TRI101/201结合部位内的疏水性所决定的.
- 一个内在的无序循环,称为"循环覆盖",影响了TRI101/201家族的疏水性结构和进化模式.
- 破坏V型酶中的疏水性增加了水的暴露,阻碍了像deoxynivalenol这样的亲水基质的结合,但不是像T-2毒素这样的疏水性基质.
- 在M型酶中强化子保持了两种基质类型的稳定性,从而达到可比的催化效率.
结论:
- TRI101/201酶的差异性催化活性主要由内在无序循环的结构灵活性及其对结合部位的疏水性子的影响来决定.
- 这种结构机制解释了观察到的催化效率对不同三合体场的变化.
- 结果提供了对酶基质相互作用的理论见解,并建议合理蛋白质设计的途径,以提高排毒能力.
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