Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition

doi:10.1126/science.aau8959

GSTDTAP > 地球科学

DOI	10.1126/science.aau8959
	Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition
	Ballinger, Elaine 1; Mosior, John 2,3; Hartman, Travis 4; Burns-Huang, Kristin 1; Gold, Ben 1; Morris, Roxanne 4; Goullieux, Laurent 5,10; Blanc, Isabelle 5,10; Vaubourgeix, Julien 1; Lagrange, Sophie 5,10; Fraisse, Laurent 5,10; Sans, Stephanie 5,10; Couturier, Cedric 5,10; Bacque, Eric 5,10; Rhee, Kyu 4; Scarry, Sarah M.6; Aube, Jeffrey 6; Yang, Guangbin 7; Ouerfelli, Ouathek 7; Schnappinger, Dirk 1; Ioerger, Thomas R.1; Engelhart, Curtis A.1; McConnell, Jennifer A.1; McAulay, Kathrine 1; Fay, Allison 9; Roubert, Christine 5,10; Sacchettini, James 2,3; Nathan, Carl 1
	2019-02-01
发表期刊	SCIENCE
ISSN	0036-8075
EISSN	1095-9203
出版年	2019
卷号	363 期号:6426 页码:498-+
文章类型	Article
语种	英语
国家	USA; France
英文摘要	Mycobacterium tuberculosis (Mtb) is the leading infectious cause of death in humans. Synthesis of lipids critical for Mtb's cell wall and virulence depends on phosphopantetheinyl transferase (PptT), an enzyme that transfers 4'-phosphopantetheine (Ppt) from coenzyme A (CoA) to diverse acyl carrier proteins. We identified a compound that kills Mtb by binding and partially inhibiting PptT. Killing of Mtb by the compound is potentiated by another enzyme encoded in the same operon, Ppt hydrolase (PptH), that undoes the PptT reaction. Thus, loss-of-function mutants of PptH displayed antimicrobial resistance. Our PptT-inhibitor cocrystal structure may aid further development of antimycobacterial agents against this long-sought target. The opposing reactions of PptT and PptH uncover a regulatory pathway in CoA physiology.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000457409400042
WOS关键词	ACYL CARRIER PROTEIN ; ESCHERICHIA-COLI ; TRANSFERASE PPTT ; CELL-WALL ; BIOSYNTHESIS ; PHOSPHODIESTERASE ; TARGET ; CRYSTALLIZATION ; PURIFICATION ; BIOCHEMISTRY
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/200663
专题	地球科学资源环境科学气候变化
作者单位	1.Weill Cornell Med, Dept Microbiol & Immunol, New York, NY 10065 USA; 2.Texas Agr & Mech Univ, Dept Biochem, College Stn, TX 77843 USA; 3.Texas Agr & Mech Univ, Dept Biophys, College Stn, TX 77843 USA; 4.Weill Cornell Med, Dept Med, New York, NY USA; 5.Sanofi, Infect Dis Therapeut Area, Marcy Letoile, France; 6.Univ N Carolina, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC USA; 7.Mem Sloan Kettering Canc Ctr, Organ Synth Core, 1275 York Ave, New York, NY 10021 USA; 8.Texas Agr & Mech Univ, Dept Comp Sci & Engn, College Stn, TX USA; 9.Mem Sloan Kettering Canc Ctr, Immunol Program, Sloan Kettering Inst, 1275 York Ave, New York, NY 10021 USA; 10.Evotec ID Lyon SAS, Marcy Letoile, France
推荐引用方式 GB/T 7714	Ballinger, Elaine,Mosior, John,Hartman, Travis,et al. Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition[J]. SCIENCE,2019,363(6426):498-+.
APA	Ballinger, Elaine.,Mosior, John.,Hartman, Travis.,Burns-Huang, Kristin.,Gold, Ben.,...&Nathan, Carl.(2019).Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition.SCIENCE,363(6426),498-+.
MLA	Ballinger, Elaine,et al."Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition".SCIENCE 363.6426(2019):498-+.