Crystal Structures of the Multidrug Binding Repressor Corynebacterium glutamicum CgmR in Complex with Inducers and with an Operator
Crystal Structures of the Multidrug Binding Repressor Corynebacterium glutamicum CgmR in Complex with Inducers and with an Operator
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DOI：
10.1016/j.jmb.2010.07.042
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发表时间：
2010-10-22
影响因子：
5.6
通讯作者：
Tanaka, Isao
中科院分区：
文献类型：
--
作者：
Itou, Hiroshi;Watanabe, Nobuhisa;Tanaka, Isao
来自谷氨棒状杆菌的CgmR （CGL2612）是一种多药耐药相关转录因子，属于TetR家族，TetR家族是一个广泛存在的细菌转录因子蛋白家族，通常参与环境反应。在这里，我们报道了CgmR同二聚体抑制因子在两个不同的诱导剂（1.95和1.4埃分辨率）和一个算子（2.5埃分辨率）的配合物中的晶体结构。CgmR-算子复合体表明，两个CgmR二聚体与算子结合，回文算子的每个半位点被DNA两侧不同二聚体的两个DNA结合域不对称地识别。诱导剂复合物表明，两种结合的诱导剂作为一个楔子，通过空间抑制改变阻遏物的操作符结合构象。当使用位阻时，如果各种药物有足够的体积来改变构象，并且它们的结合能充分降低自由能，那么它们就可以作为诱导剂。CgmR游离蛋白的结构比较研究，与操作符和诱导剂的复合物，暗示了可能有助于抑制物的多药反应的其他机制。(C) 2010 Elsevier Ltd.版权所有。
CgmR (CGL2612) from Corynebacterium glutamicum is a multidrug-resistance-related transcription factor belonging to the TetR family, which is a protein family of widespread bacterial transcription factors typically involved in environmental response. Here, we report the crystal structures of CgmR homodimeric repressor in complex with two distinct inducers (1.95 and 1.4 angstrom resolution) and with an operator (2.5 angstrom resolution). The CgmR-operator complex showed that two CgmR dimers bound to the operator, and each half-site of the palindromic operator was asymmetrically recognized by two DNA-binding domains from different dimers on the opposite sides of the DNA. The inducer complexes demonstrated that both bound inducers act as a wedge to alter the operator-binding conformation of the repressor by steric inhibition. As steric hindrance is used, various drugs should act as inducers if they have sufficient volume for the conformation change and if their bindings sufficiently reduce free energy. The comparative structural study of CgmR free protein, in complex with operator, and with inducers, implies the other mechanism that might contribute to multidrug response of the repressor. (C) 2010 Elsevier Ltd. All rights reserved.