豆蛋白衍生的乙胆酶和丁胆酶抑制的定量结构-活性关系建模
Nancy D Asen1, Chibuike C Udenigwe1,2, Rotimi E Aluko1,3
1Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
这项研究确定了抑制乙胆酶 (AChE) 和丁胆酶 (BuChE) 的中的关键氨基酸序列. 这些发现揭示了来自植物蛋白质的强效酶抑制剂的结构要求.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 蛋白质组学是指蛋白质组学.
背景情况:
- 乙胆酶 (AChE) 和丁胆酶 (BuChE) 是神经传递中的关键酶.
- 这些酶的抑制剂是阿尔茨海默氏症等疾病的重要治疗点.
- 了解的结构-活性关系对于药物设计至关重要.
研究的目的:
- 确定负责抑制AChE和BuChE的寡的特定结构特征.
- 建立基于的酶抑制剂的结构功能关系.
主要方法:
- 使用质谱学分析了从黄色田间豆蛋白消化物中识别的19种寡.
- 应用部分最小平方 (PLS) 回归来分析结构-功能关系.
- 开发用于ACHE和BuChE抑制活性的预测模型.
主要成果:
- 对ACHE抑制的9组件PLS模型显示出高的预测能力 (Q2 = 67.2%,R2 = 0.9974).
- 对BuChE抑制的模型显示出可变但显著的预测能力 (Q2 = 26.7-46.4%,R2 = 0.9577-0.9958).
- 高活性的主要残留物包括N端的Thr,Leu,Ala,Val;第二位的Asn,His,Pro,Arg;第三位的Asp,Ser;和C端的Arg.
结论:
- 特定的氨基酸组成和中的特定位置决定了ACHE和BuChE的抑制潜力.
- 确定的结构要求为设计新型抑制剂提供了基础.
- 植物衍生可以作为酶调节化合物的来源.
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