Structural Insights into the Redox-Sensing Mechanism of MarR-Type Regulator AbfR

doi:10.1021/jacs.6b11438

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	Structural Insights into the Redox-Sensing Mechanism of MarR-Type Regulator AbfR
	Liu, Guijie 1,2; Liu, Xing 1,3; Xu, Hongjiao 1,2; Liu, Xichun 4,5; Zhou, Hu3 ; Huang, Zhen 6; Gan, Jianhua 7; Chen, Hao 4,5; Lan, Lefu1 ; Yang, Cai-Guang1
刊名	JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
	2017-02-01
卷号	139 期号:4 页码:1598-1608
ISSN号	0002-7863
DOI	10.1021/jacs.6b11438
文献子类	Article
英文摘要	As a master redox-sensing MarR-family transcriptional regulator, AbfR. participates in oxidative stress responses and virulence regulations in Staphylococcus epidermidis. Here, we present structural insights into the DNA-binding mechanism of AbfR in different oxidation states by determining the X-ray crystal structures of a reduced-AbfR/ DNA complex, an overoxidized (Cys13-SO2H and Cys13-SO3H) AbfR/DNA, and 2-disulfide cross-linked AbfR dimer. Together with biochemical analyses, our results suggest that the redox regulation of Abflt,sensing displays two novel features: (i) the reversible disulfide modification, but not the irreversible overoxidation, significantly abolishes the DNA binding ability of the AbfR. repressor; (ii) either 1-disulfide cross-linked or 2-disulfide cross-linked AbfR. dimer is biologically significant. The overoxidized species of AbfR, resembling the reduced AbfR in conformation and retaining the DNA binding ability, does not exist in biologically significant concentrations, however. The 1-disulfide cross-linked modification endows AbfR with significantly weakened capability for DNA-binding. The 2-disulfide cross-linked AbfR adopts a very "open" conformation that is incompatible with DNA-binding. Overall, the concise oxidation chemistry of the redox-active cysteine allows AbfR to sense and respond to oxidative stress correctly and efficiently.
资助项目	National Natural Science Foundation of China[90913010] ; National Natural Science Foundation of China[81661138004] ; National Natural Science Foundation of China[31500110] ; National Natural Science Foundation of China[20721002] ; National Natural Science Foundation of China[91013009] ; National Key Research and Development Projects[2016YFA0501500] ; National Key Research and Development Projects[2012CB933802] ; National Key Research and Development Projects[2015CB856303]
WOS关键词	BACILLUS-SUBTILIS OHRR ; STAPHYLOCOCCUS-AUREUS ; OXIDATIVE STRESS ; SULFENIC ACID ; TRANSCRIPTIONAL REGULATORS ; ORGANIC HYDROPEROXIDES ; ANTIBIOTIC-RESISTANCE ; MAXIMUM-LIKELIHOOD ; GLOBAL REGULATOR ; FAMILY
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000393355600043
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275657]
专题	药理学第三研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yang, Cai-Guang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Lab Chem Biol, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Nanjing Univ, Inst Coordinat Chem, Nanjing 210093, Jiangsu, Peoples R China; 5.Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Coordinat Chem, Nanjing 210093, Jiangsu, Peoples R China; 6.Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA; 7.Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China
推荐引用方式 GB/T 7714	Liu, Guijie,Liu, Xing,Xu, Hongjiao,et al. Structural Insights into the Redox-Sensing Mechanism of MarR-Type Regulator AbfR[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2017,139(4):1598-1608.
APA	Liu, Guijie.,Liu, Xing.,Xu, Hongjiao.,Liu, Xichun.,Zhou, Hu.,...&Yang, Cai-Guang.(2017).Structural Insights into the Redox-Sensing Mechanism of MarR-Type Regulator AbfR.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,139(4),1598-1608.
MLA	Liu, Guijie,et al."Structural Insights into the Redox-Sensing Mechanism of MarR-Type Regulator AbfR".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 139.4(2017):1598-1608.