典型文献
Alternative Role of Motif B in Template Dependent Polymerase Inhibition
文献摘要：
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)relies on the central molecular machine RNA-dependent RNA polymerase(RdRp)for the viral replication and transcription.Remdesivir at the template strand has been shown to effectively inhibit the RNA synthe-sis in SARS-CoV-2 RdRp by deac-tivating not only the complemen-tary UTP incorporation but also the next nucleotide addition.How-ever,the underlying molecular mechanism of the second inhibitory point remains unclear.In this work,we have performed molecular dynamics simulations and demonstrated that such inhibition has not directly acted on the nucleotide addition at the active site.Instead,the translocation of Remdesivir from+1 to-1 site is hindered thermodynamically as the post-translocation state is less stable than the pre-translocation state due to the motif B residue G683.Moreover,another conserved residue S682 on motif B further hinders the dynamic translocation of Remdesivir due to the steric clash with the 1'-cyano substitution.Overall,our study has unveiled an alternative role of motif B in mediating the translocation when Remdesivir is present in the template strand and complemented our understanding about the inhibitory mechanisms exerted by Remdesivir on the RNA synthesis in SARS-CoV-2 RdRp.
文献关键词：
中图分类号：
作者姓名：
Xueying Luo;Tiantian Xu;Xin Gao;Lu Zhang
作者机构：
State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences,Fuzhou 350002,China;University of Chinese Academy of Sciences,Beijing 100049,China;Computer Science Program,Computer,Electrical and Mathematical Sciences and Engineering(CEMSE)Division,King Abdullah University of Science and Technology,Thuwal 23955-6900,King-dom of Saudi Arabia;KAUST Computational Bioscience Research Center(CBRC),King Abdullah University of Science and Technology,Thuwal 23955-6900,Kingdom of Saudi Arabia;Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry,Xiamen 361005,China
文献出处：
引用格式：
[1]Xueying Luo;Tiantian Xu;Xin Gao;Lu Zhang-.Alternative Role of Motif B in Template Dependent Polymerase Inhibition)[J].化学物理学报（英文版）,2022(03):407-412
A类：
tivating,from+1,G683,S682,clash
B类：
Alternative,Role,Motif,Template,Dependent,Polymerase,Inhibition,Severe,acute,respiratory,syndrome,coronavirus,SARS,CoV,relies,central,molecular,machine,dependent,polymerase,RdRp,viral,replication,transcription,Remdesivir,template,strand,has,been,shown,effectively,by,deac,only,tary,UTP,incorporation,but,also,next,nucleotide,addition,How,underlying,second,inhibitory,point,remains,unclear,this,work,we,have,performed,dynamics,simulations,demonstrated,that,such,inhibition,directly,acted,active,site,Instead,translocation,hindered,thermodynamically,post,state,less,stable,than,motif,residue,Moreover,another,conserved,further,hinders,steric,cyano,substitution,Overall,our,study,unveiled,alternative,role,mediating,when,present,complemented,understanding,about,mechanisms,exerted,synthesis
AB值：
0.545009
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