The arginine repressor (ArgR) regulates the expression of genes involved in arginine biosynthesis. Upon attaining a threshold concentration of arginine in the cytoplasm, the trimeric C-terminal domain of ArgR binds three arginines in a shallow surface cleft and subsequently hexamerizes forming a dimer of trimers containing six Arg co-repressor molecules which are buried at the subunit interfaces. The N-terminal domains of this complex bind to the DNA promoter thereby interrupting the transcription of the genes related to Arg biosynthesis. The crystal structures of the wild type and mutant Pro115Gln ArgR from Corynebacterium pseudotuberculosis determined at 1.7 Å demonstrate that a single amino acid substitution switches co-repressor specificity from Tyr to Arg. Molecular dynamics simulations indicate that the first step, i.e., the binding of the co-repressor, occurs in the trimeric state and that Pro115Gln ArgR preferentially binds Arg. It was also shown that, in Pro115 ArgR hexamers, the concomitant binding of sodium ions shifts selectivity to Tyr. Structural data combined with phylogenetic analyses of ArgR from C. pseudotuberculosis suggest that substitutions in the binding pocket at position 115 may alter its specificity for amino acids and that the length of the protein interdomain linker can provide further functional flexibility. These results support the existence of alternative ArgR regulatory mechanisms in this pathogenic bacterium.

中文翻译：

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单个P115Q突变可调节假结核杆菌精氨酸阻遏物的特异性。

精氨酸阻遏物（ArgR）调节精氨酸生物合成中涉及的基因的表达。在细胞质中达到精氨酸的阈值浓度时，ArgR的三聚体C末端结构域在浅表面裂口中结合三个精氨酸，随后六聚形成三聚体二聚体，其中包含六个Arg共同阻抑物分子，这些分子被掩埋在亚基界面处。该复合物的N-末端结构域与DNA启动子结合，从而中断与Arg生物合成有关的基因的转录。来自假结核棒杆菌的野生型和突变型Pro115Gln ArgR的晶体结构在1.7Å下测定，证明单个氨基酸取代将共阻遏物特异性从Tyr转换为Arg。分子动力学模拟表明第一步，即 辅助阻遏物的结合以三聚体状态发生，Pro115Gln ArgR优先结合Arg。还显示，在Pro115 ArgR六聚体中，伴随的钠离子结合将选择性转移到Tyr。结构数据与假结核梭菌ArgR的系统发育分析相结合，表明在115位结合口袋中的取代可能会改变其对氨基酸的特异性，并且蛋白域间接头的长度可提供进一步的功能灵活性。这些结果支持这种病原细菌中存在替代的ArgR调节机制。结构数据与假结核梭菌ArgR的系统发育分析相结合，表明在115位结合口袋中的取代可能会改变其对氨基酸的特异性，并且蛋白域间接头的长度可提供进一步的功能灵活性。这些结果支持这种病原细菌中存在替代的ArgR调节机制。结构数据与假结核梭菌ArgR的系统发育分析相结合，表明在115位结合口袋中的取代可能会改变其对氨基酸的特异性，并且蛋白域间接头的长度可提供进一步的功能灵活性。这些结果支持这种病原细菌中存在替代的ArgR调节机制。