Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase

doi:10.1074/jbc.M115.699801

	Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase
	He, Qing 1; Wang, Feng 1; Liu, Shiheng 1; Zhu, Deyu 1; Cong, Hengjiang 1; Gao, Fei 1; Li, Bingqing 1; Wang, Hongwei 1; Lin, Zong 2; Liao, Jun3 ; Gu, Lichuan 1
	2016-02-12
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN	0021-9258
卷号	291 期号:7 页码:3668-3681
发表状态	已发表
DOI	10.1074/jbc.M115.699801
摘要	The intracellular infections of Mycobacterium tuberculosis, which is the causative agent of tuberculosis, are regulated by many cyclic dinucleotide signaling. Rv2837c from M. tuberculosis is a soluble, stand-alone DHH-DHHA1 domain phosphodiesterase that down-regulates c-di-AMP through catalytic degradation and plays an important role in M. tuberculosis infections. Here, we report the crystal structure of Rv2837c (2.0 angstrom), and its complex with hydrolysis intermediate 5-pApA (2.35 angstrom). Our structures indicate that both DHH and DHHA1 domains are essential for c-di-AMP degradation. Further structural analysis shows that Rv2837c does not distinguish adenine from guanine, which explains why Rv2837c hydrolyzes all linear dinucleotides with almost the same efficiency. We observed that Rv2837c degraded other c-di-NMPs at a lower rate than it did on c-di-AMP. Nevertheless, our data also showed that Rv2837c significantly decreases concentrations of both c-di-AMP and c-di-GMP in vivo. Our results suggest that beside its major role in c-di-AMP degradation Rv2837c could also regulate c-di-GMP signaling pathways in bacterial cell.
关键词	cyclic diadenosine monophosphate (c-di-AMP) enzyme degradation Mycobacterium tuberculosis phosphodiesterases structure-function
收录类别	SCI ; EI
语种	英语
资助项目	Zhejiang Natural Science Foundation[LR12C05001]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000370854500044
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号	20161802327247
EI主题词	Crystal structure ; Esters ; Tubes (components)
EI分类号	Biomedical Engineering:461.1 ; Pipe, Piping and Pipelines:619.1 ; Organic Compounds:804.1 ; Crystal Lattice:933.1.1
WOS关键词	AFFECT BACTERIAL-GROWTH ; LONG-TERM SURVIVAL ; AMP PHOSPHODIESTERASE ; GMP ; IDENTIFICATION ; SPORULATION ; RESOLUTION ; REVEALS ; PROTEIN ; LEADS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1924
专题	生命科学与技术学院_PI研究组_廖军组
通讯作者	Gu, Lichuan
作者单位	1.Shandong Univ, Sch Life Sci, State Key Lab Microbial Technol, Jinan 250100, Shandong, Peoples R China 2.Tsinghua Univ, Yangtze Delta Reg Inst, Dept Biotechnol & Biomed, Jiaxing 314006, Zhejiang, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	He, Qing,Wang, Feng,Liu, Shiheng,et al. Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016,291(7):3668-3681.
APA	He, Qing.,Wang, Feng.,Liu, Shiheng.,Zhu, Deyu.,Cong, Hengjiang.,...&Gu, Lichuan.(2016).Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase.JOURNAL OF BIOLOGICAL CHEMISTRY,291(7),3668-3681.
MLA	He, Qing,et al."Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase".JOURNAL OF BIOLOGICAL CHEMISTRY 291.7(2016):3668-3681.