Computational design of serine hydrolases

• 全文链接

丝氨酸水解酶的计算设计

关键词：

来源：

science

全文链接：

//agri.nais.net.cn/topic/downloadFile/177774bf-b09f-4e32-9af4-04391b9f3f8a

来源地址：

https://www.science.org/doi/10.1126/science.adu2454

资源所属：

马铃薯基因组设计育种

类型：

学术文献

语种：

英语

原文发布日期：

2025-02-15

摘要：

The design of enzymes with complex active sites that mediate multistep reactions remains an outstanding challenge. With serine hydrolases as a model system, we combined the generative capabilities of RFdiffusion with an ensemble generation method for assessing active site preorganization to design enzymes starting from minimal active site descriptions. Experimental characterization revealed catalytic efficiencies (kcat/Km) up to 2.2x105 M−1 s−1 and crystal structures that closely match the design models (Cα RMSDs < 1 Å). Selection for structural compatibility across the reaction coordinate enabled identification of new catalysts in low-throughput screens with five different folds distinct from those of natural serine hydrolases. Our de novo approach provides insight into the geometric basis of catalysis and a roadmap for designing enzymes that catalyze multistep transformations.