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Mechanism of the allosteric regulation of Streptococcus mutans 2 '-deoxycytidylate deaminase

机译:变构调节的机制变形链球菌2》-deoxycytidylate脱氨酶

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In cells, dUMP is the intermediate precursor of dTTP in its synthesis during deoxynucleotide metabolism. In Gram-positive bacteria and eukaryotes, zinc-dependent deoxycytidylate deaminases (dCDs) catalyze the conversion of dCMP to dUMP. The activity of dCD is allosterically activated by dCTP and inhibited by dTTP. Here, the crystal structure of Streptococcus mutans dCD (SmdCD) complexed with dTTP is presented at 2.35 angstrom resolution, thereby solving the first pair of activator-bound and inhibitor-bound structures from the same species to provide a more definitive description of the allosteric mechanism. In contrast to the dTTP-bound dCD from the bacteriophage S-TIM5 (S-TIM5-dCD), dTTP-bound SmdCD adopts an inactive conformation similar to the apo form. A structural comparison suggests that the distinct orientations of the triphosphate group in S-TIM5-dCD and SmdCD are a result of the varying protein binding environment. In addition, calorimetric data establish that the modulators bound to dCD can be mutually competitively replaced. The results reveal the mechanism underlying its regulator-specific activity and might greatly enhance the understanding of the allosteric regulation of other dCDs.
机译:在细胞,转储是中间的前兆在deoxynucleotide dTTP在其合成新陈代谢。真核生物,zinc-dependent deoxycytidylate脱氨酶(以便)催化dCMP的转换转储。由dTTP dCTP激活和抑制。变异链球菌民国的晶体结构(SmdCD)包裹着dTTP呈现为2.35埃分辨率,从而解决第一一双activator-bound inhibitor-bound提供一个结构相同的物种更明确的变构的描述机制。dTTP-bound噬菌体S-TIM5 (S-TIM5-dCD)SmdCD采用活性构象相似人群的形式。不同的方向在S-TIM5-dCD和SmdCD三磷酸组不同的蛋白结合的结果环境。建立绑定dCD计划可以的调节器相互竞争所取代。揭示其机制的基础regulator-specific活动和可能很大加强对变构的理解监管其他论证。

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