文献类型：期刊文献

英文题名：Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M-tuberculosis

作者：Gao, Yun-Rong[1,2,3,9];Li, De-Feng[2,3];Fleming, Joy[1,2,3];Zhou, Ya-Feng[1];Liu, Ying[4];Deng, Jiao-Yu[5];Zhou, Lin[6];Zhou, Jie[7];Zhu, Guo-Feng[2,3];Zhang, Xian-En[2,3];Wang, Da-Cheng[2,3];Bi, Li-Jun[1,2,3,8]

机构：[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

年份：2017

卷号：7

外文期刊名：SCIENTIFIC REPORTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000406281400036)】；

基金：The authors express their appreciation to the staff at the Shanghai Synchrotron Radiation Facility of China for assistance with collecting protein diffraction data, and thank Dr. Chen Yuanyuan for technical advice and use of equipment for ITC experiments. This work was supported by grants from the National Basic Research Program of China [2011CB910300, 2013CB911500 to D.-C.W. and D.-F.L.]; the Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health [2013ZX10003006 to L.-J.B.]; the National Natural Science Foundation of China [31170132 and U1401224 to L.-J.B.]; the Chinese Academy of Sciences [KJZD-EW-TZ-L04 to X.-E.Z., and XDB08020200 to D.-C.W.], the Youth Innovation Promotion Association of the Chinese Academy of Sciences [to D.-F.L.], and the Special Fund for Public Welfare Research and Capacity Building in Guangdong Province [2014B030301002 to L.-J.B.], and the Guangdong Innovative and Entrepreneurial Research Team Program [201301S0105384179 to L.-J.B.].

语种：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.