SCO4008, a Putative TetR Transcriptional Repressor from Streptomyces coelicolor A3(2), Regulates Transcription of sco4007 by Multidrug Recognition

SCO4008, a Putative TetR Transcriptional Repressor from Streptomyces coelicolor A3(2), Regulates Transcription of sco4007 by Multidrug Recognition
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DOI:
10.1016/j.jmb.2013.06.013
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发表时间:
2013-09-23
影响因子:
5.6
通讯作者:
Tanaka, Isao
Tanaka, Isao
中科院分区:
生物学2区
文献类型:
--
作者:
Hayashi, Takeshi;Tanaka, Yoshikazu;Tanaka, Isao

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天蓝色链霉菌A3(2)的SCO 4008是TetR家族的成员。然而,其确切的功能尚不清楚。在这项研究中,以2.3埃的分辨率确定了SCO 4008的晶体结构,并分析了其与DNA结合的性质。晶体结构分析表明,SCO 4008形成一个Omega形的同源二聚体,其中单体由一个含有螺旋-转角-螺旋的N-末端DNA结合结构域和一个具有配体结合空腔的C-末端二聚体和调节结构域组成。通过指数富集和电泳迁移率变动分析的配体的基因组系统进化显示,四个SCO 4008二聚体结合到位于sco 4008和sco 4007之间的两个操纵子区域,这是属于主要促进剂超家族的二级转运蛋白。配体筛选分析表明,SCO 4008识别广泛的结构不同的阳离子和疏水化合物。这些结果表明,SCO 4008是sco 4007的转录抑制因子,与S. coelicolor A3(2). (C)2013爱思唯尔有限公司保留所有权利。
SCO4008 from Streptomyces coelicolor A3(2) is a member of the TetR family. However, its precise function is not yet clear. In this study, the crystal structure of SCO4008 was determined at a resolution of 2.3 angstrom, and its DNA-binding properties were analyzed. Crystal structure analysis showed that SCO4008 forms an Omega-shaped homodimer in which the monomer is composed of an N-terminal DNA-binding domain containing a helix-turn-helix and a C-terminal dimerization and regulatory domain possessing a ligand-binding cavity. The genomic systematic evolution of ligands by exponential enrichment and electrophoretic mobility shift assay revealed that four SCO4008 dimers bind to the two operator regions located between sco4008 and sco4007, a secondary transporter belonging to the major facilitator superfamily. Ligand screening analysis showed that SCO4008 recognizes a wide range of structurally dissimilar cationic and hydrophobic compounds. These results suggested that SCO4008 is a transcriptional repressor of sco4007 responsible for the multidrug resistance system in S. coelicolor A3(2). (C) 2013 Elsevier Ltd. All rights reserved.