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 

机构地区：[1]Department of Chemistry and Biology,Beijing University of Technology,Beijing 100124,China [2]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety,Institute of High Energy Physics,Chinese Academy of Sciences,Beijing 100049,China [3]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Chinese Chemical Letters》2022年第7期3488-3491,共4页中国化学快报（英文版）

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)。

摘　　要：Thioredoxin reductase 1(TrxR1)is over activity in tumor cell to maintain their redox balance.Although gold clusters have great potential in antitumor drug as they could well inhibit TrxR1,the molecular mechanism has not been disclosed yet.In 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 methods.We firstly inferred the binding sites of gold in the hydrophobic cavities on TrxR1.The 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 them.Our 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 studies.This work provides a new understanding of the gold clusters to inhibit TrxR1 activity.

关 键 词：Enzyme inhibition Electron transfer Thioredoxin reductase 1 Gold clusters Molecular dynamics Density functional theory 

分 类 号：TQ460.1[化学工程—制药化工]