Structural analysis of the regulatory mechanism of marr protein rv2887 in m-tuberculosis
文献类型:期刊论文
作者 | Gao, Yun-Rong1,2,3,9; Li, De-Feng2,3; Fleming, Joy1,2,3; Zhou, Ya-Feng1; Liu, Ying4; Deng, Jiao-Yu5; Zhou, Lin6; Zhou, Jie7; Zhu, Guo-Feng2,3; Zhang, Xian-En2,3 |
刊名 | Scientific reports
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出版日期 | 2017-07-25 |
卷号 | 7页码:13 |
ISSN号 | 2045-2322 |
DOI | 10.1038/s41598-017-01705-4 |
通讯作者 | Wang, da-cheng(dcwang@ibp.ac.cn) ; Bi, li-jun(blj@ibp.ac.cn) |
英文摘要 | Marr family proteins are transcriptional regulators that control expression of bacterial proteins involved in metabolism, virulence, stress responses and multi-drug resistance, mainly via ligandmediated attenuation of dna binding. greater understanding of their underlying regulatory mechanism may open up new avenues for the effective treatment of bacterial infections. to gain molecular insight into the mechanism of rv2887, a marr family protein in m. tuberculosis, we first showed that it binds salicylate (sa) and para-aminosalicylic acid (pas), its structural analogue and an antitubercular drug, in a 1: 1 stoichiometry with high affinity. subsequent determination and analysis of rv2887 crystal structures in apo form, and in complex with sa, pas and dna showed that sa and pas bind to rv2887 at similar sites, and that rv2887 interacts with dna mainly by insertion of helix alpha 4 into the major groove. ligand binding triggers rotation of the whth domain of rv2887 toward the dimerization domain, causing changes in protein conformation such that it can no longer bind to a 27 bp recognition sequence in the upstream region of gene rv0560c. the structures provided here lay a foundation for the design of small molecules that target rv2887, a potential new approach for the development of anti-mycobacterials. |
WOS关键词 | FAMILY TRANSCRIPTIONAL REGULATOR ; DNA-BINDING MECHANISM ; MULTIPLE ANTIBIOTIC-RESISTANCE ; CRYSTAL-STRUCTURE REVEALS ; ESCHERICHIA-COLI ; VIRULENCE ; NETWORK ; GENE ; TETRACYCLINE ; EXPRESSION |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
语种 | 英语 |
WOS记录号 | WOS:000406281400036 |
出版者 | NATURE PUBLISHING GROUP |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373365 |
专题 | 武汉病毒研究所 |
通讯作者 | Wang, Da-Cheng; Bi, Li-Jun |
作者单位 | 1.Foshan Univ, Sch Stomatol & Med, Foshan 528000, Guangdong, Peoples R China 2.Chinese Acad Sci, Key Lab RNA Biol, Beijing 100101, Peoples R China 3.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 4.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China 5.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China 6.Ctr TB Control Guangdong Prov, Guangzhou 51630, Guangdong, Peoples R China 7.4th Peoples Hosp, Foshan 528000, Guangdong, Peoples R China 8.Guangdong Prov Key Lab TB Syst Biol & Translat M, Foshan 528000, Guangdong, Peoples R China 9.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
推荐引用方式 GB/T 7714 | Gao, Yun-Rong,Li, De-Feng,Fleming, Joy,et al. Structural analysis of the regulatory mechanism of marr protein rv2887 in m-tuberculosis[J]. Scientific reports,2017,7:13. |
APA | Gao, Yun-Rong.,Li, De-Feng.,Fleming, Joy.,Zhou, Ya-Feng.,Liu, Ying.,...&Bi, Li-Jun.(2017).Structural analysis of the regulatory mechanism of marr protein rv2887 in m-tuberculosis.Scientific reports,7,13. |
MLA | Gao, Yun-Rong,et al."Structural analysis of the regulatory mechanism of marr protein rv2887 in m-tuberculosis".Scientific reports 7(2017):13. |
入库方式: iSwitch采集
来源:武汉病毒研究所
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