Biochemical characterization and ligand-binding properties of trehalose-6-phosphate phosphatase from Mycobacterium tuberculosis

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	Biochemical characterization and ligand-binding properties of trehalose-6-phosphate phosphatase from Mycobacterium tuberculosis
	Shi, Lina ; Zhang, Haiping ; Qiu, Yu ; Wang, Qian ; Wu, Xueji ; Wang, Honghai ; Zhang, Xuelian ; Lin, Donghai ; Wang Q(王骞) ; Wu XJ(吴学记) ; Lin DH(林东海)
刊名	http://dx.doi.org/10.1093/abbs/gmt084
	2013
关键词	PROTEIN SECONDARY STRUCTURE CIRCULAR-DICHROISM TREHALOSE BIOSYNTHESIS I-TASSER PREDICTION SMEGMATIS PATHWAY
英文摘要	National Natural Science Foundation of China [31170717, 91129713, 31270777]; Trehalose-6-phosphate phosphatase (TPP) is an essential enzyme for growth of mycobacteria, which has been identified to be a potential anti-tuberculosis drug target. However, the biochemical and ligand-binding properties and the 3D structure of TPP remain unclear so far. In the present study, we expressed the recombinant TPP protein from Mycobacterium tuberculosis (otsB2/Rv3372). Results from the far-ultraviolet circular dichroism experiments indicated that the secondary structure of TPP was rich in -helix with a lower structural stability (C-m 2.099 0.134 M). Ligand-binding assay by isothermal titration calorimetry demonstrated that the recombinant TPP protein could bind with trehalose-6-P in the presence of Mg-2 (K-d 39.52 1.78 M) with a molar ratio of 1 : 1. In addition, the 3D structure of TPP was modeled by I-TASSER, indicating that the TPP protein was composed of a hydrolase domain, a cap domain, and an N-terminal domain. Flexible docking was further conducted by using the Simulations/Dock module of the Molecular Operating Environment software. The binding pocket of TPP for both trehalose-6-P and Mg-2 was determined, which was located on the interface between the hydrolase domain and the cap domain. Asp149, Gly186, Arg187, Arg291, and Glu295 were identified to be the key residues for TPP binding with trehalose-6-P. This work may lay the basis for further structural and functional studies of TPP and TPP-related novel drug development.
语种	英语
出版者	OXFORD UNIV PRESS
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93486]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Shi, Lina,Zhang, Haiping,Qiu, Yu,et al. Biochemical characterization and ligand-binding properties of trehalose-6-phosphate phosphatase from Mycobacterium tuberculosis[J]. http://dx.doi.org/10.1093/abbs/gmt084,2013.
APA	Shi, Lina.,Zhang, Haiping.,Qiu, Yu.,Wang, Qian.,Wu, Xueji.,...&林东海.(2013).Biochemical characterization and ligand-binding properties of trehalose-6-phosphate phosphatase from Mycobacterium tuberculosis.http://dx.doi.org/10.1093/abbs/gmt084.
MLA	Shi, Lina,et al."Biochemical characterization and ligand-binding properties of trehalose-6-phosphate phosphatase from Mycobacterium tuberculosis".http://dx.doi.org/10.1093/abbs/gmt084 (2013).