对于UGTs的有效计算策略 催化函数预测
Nianhang Chen1, Zhennan Jiang2, Zhekai Xie1
1School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
ACS synthetic biology
|May 16, 2025
概括
糖转移酶 (UGTs) 是天然产品合成的关键. 一种新的计算方法准确地预测了UGT功能和基质特异性,区分了类似的三烯酸和类固醇氨酸.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 葡萄糖转移酶 (GTs) 是合成药理活性天然产品 (如沙素) 的重要酶.
- 在GT-B家族酶中区分基质特异性,特别是在结构相似的三类和类固醇沙因中,是具有挑战性的.
- 了解酶机制和基质相互作用对于药物发现和酶工程至关重要.
研究的目的:
- 阐明基质运输机制和N终端域 (NTD) 在GT-B糖转移酶中的作用.
- 开发一种计算方法来分类植物性UGT并预测它们的基质特异性.
- 区分作用于结构相似的三基和类固醇基质的UGT.
主要方法:
- 在PpUGT73CR1.1.中进行分子动力学模拟以揭示基质运输道和机制.
- 在44种植物性UGT中分析结合性口袋残留物.
- 使用ESM2蛋白模型特征和PCA集群的基于快速序列的分类方法的开发.
- 计算预测的实验验证.
主要成果:
- 为GT-B酶提出了一个合理的基质运输机制,涉及NTD调节.
- 对于固醇UGTs,在活性部位残留物中发现了明显的模式.
- 基于序列的方法准确地分类了UGT和差异化基质特异性,即使对于密切相关的化合物.
- 计算预测通过实验测试成功验证.
结论:
- 这项研究为GT-B酶基质结合和运输机制提供了新的见解.
- 已经开发出一种计算效率高,准确的方法来预测UGT函数和基质特异性.
- 这项工作为未知的UGT的功能注释提供了宝贵的工具,并有助于发现新型天然产品.
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