化学
木瓜蛋白酶
立体化学
核磁共振波谱
结合位点
蛋白酶
冠状病毒
构象变化
共价键
生物化学
生物物理学
酶
2019年冠状病毒病(COVID-19)
有机化学
传染病(医学专业)
病理
生物
医学
疾病
作者
Yutaro Shiraishi,Ichio Shimada
摘要
Papain-like protease (PLpro) from severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a prime target for the development of antivirals for Coronavirus disease 2019 (COVID-19). However, drugs that target the PLpro protein have not yet been approved. In order to gain insights into the development of a PLpro inhibitor, conformational dynamics of PLpro in complex with GRL0617, the most well-characterized PLpro inhibitor, were investigated using nuclear magnetic resonance (NMR) spectroscopy in solution. Although mutational analyses demonstrated that the L162 sidechain interaction is responsible for the affinity for GRL0617, NMR analyses revealed that L162 in the inhibitor-binding pocket underwent conformational exchange and was not fixed in the conformation in which it formed a contact with ortho-methyl group of GRL0617. The identified conformational dynamics would provide a rationale for the binding mechanism of a covalent inhibitor designed based on GRL0617.
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