Crystal structure of the Vibrio cholerae VqmA-ligand-DNA complex provides insight into ligand-binding mechanisms relevant for drug design

doi:10.1074/jbc.RA118.006082

CORC > 上海应用物理研究所 > 中国科学院上海应用物理研究所 > 中科院上海应用物理研究所2011-2017年

	Crystal structure of the Vibrio cholerae VqmA-ligand-DNA complex provides insight into ligand-binding mechanisms relevant for drug design
	Wu, H ; Li, MJ ; Guo, HJ ; Zhou, H ; Li, B ; Xu, Q ; Xu, CY ; Yu, F ; He, JH
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2019
卷号	294 期号:8 页码:2580—2592
关键词	TO-CELL COMMUNICATION LUXR-LUXI FAMILY QUORUM PROTEIN EXPRESSION REGULATOR AUTOINDUCER REPRESSION FEATURES DOMAIN
DOI	10.1074/jbc.RA118.006082
文献子类	期刊论文
英文摘要	VqmA is a highly conserved transcriptional regulator of the quorum-sensing system of Vibrio cholerae, a major human pathogen that continues to imperil human health. VqmA represses biofilm formation and plays an important role in V. cholerae pathogenicity in the human host. Although VqmA's biological function is well understood, the molecular mechanisms by which its specific ligand (and effector), 3,5-dimethylpyrazine-2-ol (DPO), controls transcription of the target gene, vqmR, remain obscure. To elucidate the molecular mechanism of DPO binding, we used structural analyses and biochemical assays to study the V. cholerae VqmA-DPO-DNA complex. These analyses revealed that VqmA contains an N-terminal homodimer domain (PAS) and a C-terminal DNA-binding domain (DBD). We observed that VqmA directly binds to a DPO molecule via a compact hydrophobic pocket, consisting of a six-stranded antiparallel beta-sheet and several alpha-helices. We also found that the VqmA dimer interacts with the quasi-palindromic sequence of the vqmR promoter through its DBD. The results of the biochemical studies indicated that a water atom and VqmA residues Phe-67 and Lys-101 play a key role in effector recognition, which is also assisted by Tyr-36 and Phe-99. This is the first molecular level view of the VqmA dimer bound to DPO and DNA. The structure-function analyses presented here improve our understanding of the complex mechanisms in the transcriptional regulation of VqmA in Vibrio spp. and may inform the design of drugs to manage V. cholerae infections.
语种	英语
内容类型	期刊论文
源URL	[http://ir.sinap.ac.cn/handle/331007/31537]
专题	上海应用物理研究所_中科院上海应用物理研究所2011-2017年
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai 201800, Peoples R China;
推荐引用方式 GB/T 7714	Wu, H,Li, MJ,Guo, HJ,et al. Crystal structure of the Vibrio cholerae VqmA-ligand-DNA complex provides insight into ligand-binding mechanisms relevant for drug design[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(8):2580—2592.
APA	Wu, H.,Li, MJ.,Guo, HJ.,Zhou, H.,Li, B.,...&He, JH.(2019).Crystal structure of the Vibrio cholerae VqmA-ligand-DNA complex provides insight into ligand-binding mechanisms relevant for drug design.JOURNAL OF BIOLOGICAL CHEMISTRY,294(8),2580—2592.
MLA	Wu, H,et al."Crystal structure of the Vibrio cholerae VqmA-ligand-DNA complex provides insight into ligand-binding mechanisms relevant for drug design".JOURNAL OF BIOLOGICAL CHEMISTRY 294.8(2019):2580—2592.