ACAT2 x-ray

Phenotypic screening identified a site-specific (Y237) and regioselective SuPUR ligand of ACAT2 to reveal an unexpected metabolic dependency in cancer cells. A crystal structure of SuPUR ligand-bound ACAT2 revealed the purine group binds deep in the CoA pocket forming key interactions with catalytic residues via a water bridge to guide future structure-based ligand design.

表型筛选鉴定出一种针对酰基辅酶A胆固醇酰基转移酶2（ACAT2）的位点特异性（Y237）且区域选择性的SuPUR配体，该配体揭示了癌细胞中一种此前未被发现的代谢依赖性。SuPUR配体结合的ACAT2晶体结构显示，其嘌呤基团深入结合于辅酶A（Coenzyme A, CoA）口袋中，并通过水桥与催化残基形成关键相互作用，可为未来基于结构的配体设计提供指导。