气候变化领域集成服务门户(CCPortal): The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic

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DOI	10.1073/pnas.2016705118
	The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic
	Feng L.; Mundy J.E.A.; Stevenson C.E.M.; Mitchenall L.A.; Lawson D.M.; Mi K.; Maxwell A.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	DNA gyrase, a type II topoisomerase, introduces negative supercoils into DNA using ATP hydrolysis. The highly effective gyrasetargeted drugs, fluoroquinolones (FQs), interrupt gyrase by stabilizing a DNA-cleavage complex, a transient intermediate in the supercoiling cycle, leading to double-stranded DNA breaks. MfpA, a pentapeptide-repeat protein in mycobacteria, protects gyrase from FQs, but its molecular mechanism remains unknown. Here, we show that Mycobacterium smegmatis MfpA (MsMfpA) inhibits negative supercoiling by M. smegmatis gyrase (Msgyrase) in the absence of FQs, while in their presence, MsMfpA decreases FQinduced DNA cleavage, protecting the enzyme from these drugs. MsMfpA stimulates the ATPase activity of Msgyrase by directly interacting with the ATPase domain (MsGyrB47), which was confirmed through X-ray crystallography of the MsMfpA-MsGyrB47 complex, and mutational analysis, demonstrating that MsMfpA mimics a T (transported) DNA segment. These data reveal the molecular mechanism whereby MfpA modulates the activity of gyrase and may provide a general molecular basis for the action of other pentapeptide-repeat proteins. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNA gyrase; Fluoroquinolones; Pentapeptide-repeat proteins; Topoisomerase; Tuberculosis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180247
作者单位	Department of Biological Chemistry, John Innes Centre, Norwich, NR4 7UH, United Kingdom; Chinese Academy of Sciences, Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, China
推荐引用方式 GB/T 7714	Feng L.,Mundy J.E.A.,Stevenson C.E.M.,et al. The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic[J],2021,118(11).
APA	Feng L..,Mundy J.E.A..,Stevenson C.E.M..,Mitchenall L.A..,Lawson D.M..,...&Maxwell A..(2021).The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Feng L.,et al."The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).