Yamazoe Yasushi, Murayama Norie
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan.
Division of Risk Assessment, National Institute of Health Sciences, Tonomachi 3-25-26, Kawasaki-ku, Kawasaki 210-9501, Japan.
Food Saf (Tokyo). 2024 Dec 20;12(4):69-82. doi: 10.14252/foodsafetyfscj.D-24-00010. eCollection 2024 Dec.
A Template system for the understanding of human CYP2J2-mediated reactions was constructed from the assembly of the ligands with the introduction of ideas of allowable width, Trigger-residue and the residue-initiated movement of ligands in the active site, which were in common with other Template* systems for human CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, CYP3A4, CYP3A5, and CYP3A7 (Drug Metab Pharmacokinet 2016, 2017, 2019, 2020, 2021, 2022, 2023, 2024, and in press 2024). CYP2J2 system also includes ideas of bi-molecule binding of ligands on the Template. From their placements on the Template and rules for interaction modes, verifications of good and poor substrates, regio/stereo-selectivity, and inhibitory interaction became available faithfully for these ligands. The refined CYP2J2-Template system will thus offer reliable estimations of this human CYP catalysis toward ligands of diverse structures, together with their deciphering information to lead to judgments.
通过引入允许宽度、触发残基以及配体在活性位点的残基引发移动等概念，将配体进行组装，构建了一个用于理解人类CYP2J2介导反应的模板系统，这些概念与用于人类CYP1A1、CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C18、CYP2C19、CYP2E1、CYP3A4、CYP3A5和CYP3A7的其他模板系统相同（《药物代谢与药代动力学》，2016年、2017年、2019年、2020年、2021年、2022年、2023年、2024年及即将发表的2024年）。CYP2J2系统还包括配体在模板上的双分子结合概念。根据它们在模板上的位置和相互作用模式规则，可以如实地验证这些配体的优劣底物、区域/立体选择性以及抑制性相互作用。因此，经过完善的CYP2J2模板系统将能够可靠地估计这种人类CYP对各种结构配体的催化作用，并提供其解读信息以进行判断。
