Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria

doi:10.1073/pnas.2002835117

	Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria
	Chen, Xiaobo1,2,3 ; Chen, Jiayue 1; Yan, Bing 1; Zhang, Wei 1; Guddat, Luke W.4; Liu, Xiang 1; Rao, Zihe1,2,3,5,6
	2020-07-14
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (IF:9.4[JCR-2023],10.8[5-Year])
ISSN	0027-8424
卷号	117 期号:28 页码:16324-16332
发表状态	已发表
DOI	10.1073/pnas.2002835117
摘要	FadE, an acyl-CoA dehydrogenase, introduces unsaturation to car-bon chains in lipid metabolism pathways. Here, we report that FadE5 from Mycobacterium tuberculosis (MtbFadE5) and Mycobac-terium smegmatis (MsFadE5) play roles in drug resistance and ex-hibit broad specificity for linear acyl-CoA substrates but have a preference for those with long carbon chains. Here, the structures of MsFadE5 and MtbFadE5, in the presence and absence of sub-strates, have been determined. These reveal the molecular basis for the broad substrate specificity of these enzymes. FadE5 inter-acts with the CoA region of the substrate through a large number of hydrogen bonds and an unusual pi-pi stacking interaction, allowing these enzymes to accept both short-and long-chain sub-strates. Residues in the substrate binding cavity reorient their side chains to accommodate substrates of various lengths. Longer carbon-chain substrates make more numerous hydrophobic inter-actions with the enzyme compared with the shorter-chain sub-strates, resulting in a preference for this type of substrate.
关键词	tuberculosis mycobacteria acyl-CoA dehydrogenase fatty acid
收录类别	SCI ; SCIE
语种	英语
资助项目	National Key Research & Development Program of China[2017YFC0840300] ; National Natural Science Foundation of China[81520108019] ; Fundamental Research Funds for the Central Universities, Nankai University[63191431][63181333]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000553289400007
出版者	NATL ACAD SCIENCES
WOS关键词	RAT-LIVER MITOCHONDRIA ; STRUCTURE REFINEMENT ; CRYSTAL-STRUCTURES ; BETA-OXIDATION ; MEDIUM-CHAIN ; TUBERCULOSIS ; COENZYME ; IDENTIFICATION ; PURIFICATION ; METABOLISM
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/122672
专题	免疫化学研究所_特聘教授组_饶子和组生命科学与技术学院
通讯作者	Liu, Xiang
作者单位	1.Nankai Univ, Coll Life Sci, Frontiers Sci Ctr Cell Responses, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China 2.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia 5.Tsinghua Univ, Lab Struct Biol, Beijing 100084, Peoples R China 6.Chinese Acad Sci, Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China
第一作者单位	免疫化学研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Chen, Xiaobo,Chen, Jiayue,Yan, Bing,et al. Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2020,117(28):16324-16332.
APA	Chen, Xiaobo.,Chen, Jiayue.,Yan, Bing.,Zhang, Wei.,Guddat, Luke W..,...&Rao, Zihe.(2020).Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,117(28),16324-16332.
MLA	Chen, Xiaobo,et al."Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 117.28(2020):16324-16332.