南方科技大学知识苑(SUSTech KC): Structural basis for the inhibition mechanism of the DNA polymerase holoenzyme from mpox virus

题名	Structural basis for the inhibition mechanism of the DNA polymerase holoenzyme from mpox virus
作者	Shen, Yaping 1; Li, Yaning 3; Yan, Renhong2
通讯作者	Yan, Renhong
发表日期	2024-06-06
DOI	10.1016/j.str.2024.03.004
发表期刊	STRUCTURE 影响因子和分区
ISSN	0969-2126
EISSN	1878-4186
卷号	32 期号:6
摘要	There are three key components at the core of the mpox virus (MPXV) DNA polymerase holoenzyme: DNA polymerase F8, processivity factors A22, and the Uracil-DNA glycosylase E4. The holoenzyme is recognized as a vital antiviral target because MPXV replicates in the cytoplasm of host cells. Nucleotide analogs such as cidofovir and cytarabine (Ara -C) have shown potential in curbing MPXV replication and they also display promise against other poxviruses. However, the mechanism behind their inhibitory effects remains unclear. Here, we present the cryo-EM structure of the DNA polymerase holoenzyme F8/A22/E4 bound with its competitive inhibitor Ara -C -derived cytarabine triphosphate (Ara-CTP) at an overall resolution of 3.0 A & ring; and reveal its inhibition mechanism. Ara-CTP functions as a direct chain terminator in proximity to the deoxycytidine triphosphate (dCTP)-binding site. The extra hydrogen bond formed with Asn665 makes it more potent in binding than dCTP. Asn665 is conserved among eukaryotic B -family polymerases.
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	通讯
资助项目	Major Talent Recruitment Program of Guangdong Province[2021QNO2Y167] ; National Natural Science Foundation of China[82202517]
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS记录号	WOS:001251267200001
出版者	CELL PRESS
ESI学科分类	BIOLOGY & BIOCHEMISTRY
来源库	Web of Science
引用统计
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/787566
专题	南方科技大学医学院_生物化学系南方科技大学医学院
作者单位	1.Westlake Univ, Key Lab Struct Biol Zhejiang Prov, Westlake Lab Life Sci & Biomed, Ctr Infect Dis Res,Sch Life Sci, Hangzhou 310024, Zhejiang, Peoples R China 2.Southern Univ Sci & Technol, Key Univ Lab Metab & Hlth Guangdong, Sch Med, Dept Biochem, Shenzhen 518055, Guangdong, Peoples R China 3.Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Tsinghua Peking Joint Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China
通讯作者单位	生物化学系; 南方科技大学医学院
推荐引用方式 GB/T 7714	Shen, Yaping,Li, Yaning,Yan, Renhong. Structural basis for the inhibition mechanism of the DNA polymerase holoenzyme from mpox virus[J]. STRUCTURE,2024,32(6).
APA	Shen, Yaping,Li, Yaning,&Yan, Renhong.(2024).Structural basis for the inhibition mechanism of the DNA polymerase holoenzyme from mpox virus.STRUCTURE,32(6).
MLA	Shen, Yaping,et al."Structural basis for the inhibition mechanism of the DNA polymerase holoenzyme from mpox virus".STRUCTURE 32.6(2024).