Cysteine thiol-based transcriptional regulators orchestrate the coordinated regulation of redox homeostasis and other cellular processes by ‘sensing’ or detecting a specific redox-active molecule, which in turn activates the transcription of a specific detoxification pathway. The extent to which these sensors are truly specific in cells for a singular class of reactive small-molecule stressors, for example, reactive oxygen or sulfur species, is largely unknown. Here, we report structural and mechanistic insights into the thiol-based transcriptional repressor SqrR, which reacts exclusively with oxidized sulfur species such as persulfides, to yield a tetrasulfide bridge that inhibits DNA operator–promoter binding. Evaluation of crystallographic structures of SqrR in various derivatized states, coupled with the results of a mass spectrometry-based kinetic profiling strategy, suggest that persulfide selectivity is determined by structural frustration of the disulfide form. These findings led to the identification of an uncharacterized repressor from the bacterial pathogen Acinetobacter baumannii as a persulfide sensor.

基于半胱氨​​酸硫醇的转录调节剂通过“感知”或检测特定的氧化还原活性分子来协调氧化还原稳态和其他细胞过程的协调调节，进而激活特定解毒途径的转录。这些传感器在细胞中对一类单一的反应性小分子应激物（例如，活性氧或硫物质）的真正特异性程度在很大程度上是未知的。在这里，我们报告了对基于硫醇的转录阻遏物 SqrR 的结构和机制见解，SqrR 仅与氧化硫物质（如过硫化物）反应，以产生抑制 DNA 操纵子-启动子结合的四硫键。评估 SqrR 在各种衍生状态下的晶体结构，结合基于质谱的动力学分析策略的结果，表明过硫化物的选择性是由二硫化物形式的结构挫折决定的。这些发现导致从细菌病原体中鉴定出一种未表征的阻遏物鲍曼不动杆菌作为过硫化物传感器。