Broken electron transfer pathway in enzyme:Gold clusters inhibiting TrxR1/Trx via cell studies and theory simulations

作     者：Wenchao Niu Zhongying Du Chunyu Zhang Deting Xu Jiaojiao Li Minghui Sun Liyuan Wu Haodong Yao Lina Zhao Xueyun Gao Wenchao Niu;Zhongying Du;Chunyu Zhang;Deting Xu;Jiaojiao Li;Minghui Sun;Liyuan Wu;Haodong Yao;Lina Zhao;Xueyun Gao

作者机构：Department of Chemistry and BiologyBeijing University of TechnologyBeijing 100124China CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyInstitute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of SciencesBeijing 100049China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2022年第33卷第7期

页      面：3488-3491页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：financially supported by the National Science Foundation of China(Nos.21727817,U2067214,11621505,31971311) the National Key Basic Research Program of China(No.2020YFA0710700) 

主　　题：Enzyme inhibition Electron transfer Thioredoxin reductase 1 Gold clusters Molecular dynamics Density functional theory 

摘      要：Thioredoxin reductase 1(TrxR1)is over activity in tumor cell to maintain their redox *** gold clusters have great potential in antitumor drug as they could well inhibit TrxR1,the molecular mechanism has not been disclosed *** this work,we revealed gold clusters can well inhibit the activity of TrxR1 in lung tumor cells and further disclosed the inhibition mechanism by using computational simulation *** firstly inferred the binding sites of gold in the hydrophobic cavities on *** simulation results show that the gold ion(released from Au cluster)interact with–SH of Cys189 in TrxR1,this greatly increase the distance between the C-terminal redox center of TrxR1 and the Trx redox center,thereby destroy the electron transfer pathway between *** electron transfer destroying mechanism is different from the previous hypothesis that gold binds to the Sec498 of TrxR1 which has never been proved by experimental and theory *** work provides a new understanding of the gold clusters to inhibit TrxR1 activity.