双加氧酶
酶
生物化学
药物发现
活动站点
立体化学
化学
生物
结合位点
小分子
计算生物学
作者
Hong‐Yan Lin,Jin Dong,Jiangqing Dong,Wen‐Chao Yang,Guang‐Fu Yang
标识
DOI:10.1016/j.tibs.2023.02.006
摘要
4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays a key role in tyrosine metabolism and has been identified as a promising target for herbicide and drug discovery. The structures of HPPD complexed with different types of inhibitors have been determined previously. We summarize the structures of HPPD complexed with structurally diverse molecules, including inhibitors, natural products, substrates, and catalytic intermediates; from these structures, the detailed inhibitory mechanisms of different inhibitors were analyzed and compared, and the key structural factors determining the slow-binding behavior of inhibitors were identified. Further, we propose four subpockets that accommodate different inhibitor substructures. We believe that these analyses will facilitate in-depth understanding of the enzymatic reaction mechanism and enable the design of new inhibitors with higher potency and selectivity.
科研通智能强力驱动
Strongly Powered by AbleSci AI