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

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• 作者：Yanhua Li ; Zhen Guo ; Li Jin ; Deqiang Wang ; Zengqiang Gao ; Xiaodong Su ; Haifeng Hou and Yuhui Dong
• 关键词：allosteric regulation ; crystal structure ; enzyme inactivation ; enzyme mechanism ; enzyme structure ; 2&prime ; -deoxycytidylate deaminase ; Streptococcus mutans
• 刊名：Acta Crystallographica Section D
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：72
• 期：7
• 页码：883-891
• 全文大小：1940K
• ISSN：1399-0047

文摘

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 Å 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.