Crystal structure of L-glutamate N-acetyltransferase ArgA from Mycobacterium tuberculosis

doi:10.1016/j.bbapap.2017.09.009

	Crystal structure of L-glutamate N-acetyltransferase ArgA from Mycobacterium tuberculosis
	Yang, Xiuna 1; Wu, Lijie 1; Ran, Yajun1,2,3 ; Xu, Ao 4; Zhang, Bing1,2,3 ; Yang, Xiaolin1,2,3 ; Zhang, Rongguang 1; Rao, Zihe1,2 ; Li, Jun 1
	2017-12
发表期刊	BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS (IF:2.5[JCR-2023],2.8[5-Year])
ISSN	1570-9639
卷号	1865 期号:12 页码:1800-1807
发表状态	已发表
DOI	10.1016/j.bbapap.2017.09.009
摘要	L-arginine is used as a source of both carbon and nitrogen in Mycobacterium tuberculosis (Mtb) and its biosynthesis is essential for the pathogen's survival. MtbArgA (Rv2747) catalyzes the initial step in L-arginine biosynthesis by transferring an acetyl group from acetyl coenzyme A (AcCoA) to L-glutamate. MtbArgA is a class III N-acetylglutamate synthase (NAGS) with no structural information. Here, we solved the crystal structure of MtbArgA complexed with AcCoA and L-glutamate. The overall structure adopts a classic fold of the GCN5-related N-acetyltransferase (GNAT) family, characterized by a "V"-shaped cleft and 13-bulge, but uses distinct residues for the binding and reaction of AcCoA. In particular, its activity depends on dimerization to form a deep, vast pocket for L-glutamate binding. Interestingly, in the structure, L-glutamate binds at a site far away from AcCoA, implying a mechanism of separate capture and catalysis. Additionally, based on a docking model of L-glutamate at the catalytic site, a one-step sequential mechanism was proposed for enzymatic catalysis. Important sites for substrate binding and catalysis were also evaluated by site-directed mutagenesis study and activity analysis. The unique features of the MtbArgA structure will provide useful insights for inhibitor design and anti-tuberculosis drug discovery.
关键词	Acetyl coenzyme A Glutamate Acetyltransferase Crystal structure Mycobacterium tuberculosis
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation[31300058] ; National Natural Science Foundation[31500607]
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
WOS类目	Biochemistry & Molecular Biology ; Biophysics
WOS记录号	WOS:000414110000008
出版者	ELSEVIER SCIENCE BV
WOS关键词	ARGININE-BIOSYNTHESIS ; PROTEIN-STRUCTURE ; MOLECULAR-BASIS ; ACETYL CYCLE ; GENE ; ACETYLGLUTAMATE ; METABOLISM ; MECHANISMS ; EVOLUTION ; BACTERIA
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/9929
专题	生命科学与技术学院免疫化学研究所_特聘教授组_饶子和组生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Li, Jun
作者单位	1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, Natl Ctr Prot Sci Shanghai,Shanghai Sci Res Ctr, 333 Haike Rd, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Nankai Univ, Tianjin Key Lab Prot Sci, Coll Life Sci, Tianjin 300071, Peoples R China
推荐引用方式 GB/T 7714	Yang, Xiuna,Wu, Lijie,Ran, Yajun,et al. Crystal structure of L-glutamate N-acetyltransferase ArgA from Mycobacterium tuberculosis[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2017,1865(12):1800-1807.
APA	Yang, Xiuna.,Wu, Lijie.,Ran, Yajun.,Xu, Ao.,Zhang, Bing.,...&Li, Jun.(2017).Crystal structure of L-glutamate N-acetyltransferase ArgA from Mycobacterium tuberculosis.BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,1865(12),1800-1807.
MLA	Yang, Xiuna,et al."Crystal structure of L-glutamate N-acetyltransferase ArgA from Mycobacterium tuberculosis".BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 1865.12(2017):1800-1807.