Mechanism of the allosteric regulation of Streptococcus mutans 2 '-deoxycytidylate deaminase
文献类型：期刊论文
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| 作者 | Li YH(李艳华) ; Gao ZQ(高增强); Li, YH; Guo, Z; Jin, L; Wang, DQ; Gao, ZQ; Su, XD; Hou, HF; Dong, YH
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| 刊名 | ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
 ; ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
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| 出版日期 | 2016 ; 2016 |
| 卷号 | 72期号:7页码:883-891 |
| 关键词 | allosteric regulation allosteric regulation crystal structure enzyme inactivation enzyme mechanism enzyme structure 2 '-deoxycytidylate deaminase Streptococcus mutans crystal structure enzyme inactivation enzyme mechanism enzyme structure 2 '-deoxycytidylate deaminase Streptococcus mutans |
| DOI | 10.1107/S2059798316009153 ; 10.1107/S2059798316009153 |
| 通讯作者 | 董宇辉 ; 董宇辉 |
| 文献子类 | 期刊论文 |
| 英文摘要 | 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.; 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. |
| WOS关键词 | HUMAN DEOXYCYTIDYLATE DEAMINASE ; HEPATITIS-B-VIRUS ; CYTIDINE DEAMINASE ; CRYSTAL-STRUCTURE ; DNTP POOLS ; SUBSTRATE ; INHIBITOR ; SUBUNIT ; COMPLEX ; BINDING |
| 语种 | 英语 ; 英语 |
| WOS记录号 | WOS:000379912500007 ; WOS:000379912500007 |
| 源URL | [http://ir.ihep.ac.cn/handle/311005/260448]  |
| 专题 | 高能物理研究所_多学科研究中心 |
| 作者单位 | 中国科学院高能物理研究所 |
| 推荐引用方式 GB/T 7714 | Li YH,Gao ZQ,Li, YH,et al. Mechanism of the allosteric regulation of Streptococcus mutans 2 '-deoxycytidylate deaminase, Mechanism of the allosteric regulation of Streptococcus mutans 2 '-deoxycytidylate deaminase[J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY,2016, 2016,72, 72(7):883-891, 883-891. |
| APA | 李艳华.,高增强.,Li, YH.,Guo, Z.,Jin, L.,...&董宇辉.(2016).Mechanism of the allosteric regulation of Streptococcus mutans 2 '-deoxycytidylate deaminase.ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY,72(7),883-891. |
| MLA | 李艳华,et al."Mechanism of the allosteric regulation of Streptococcus mutans 2 '-deoxycytidylate deaminase".ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY 72.7(2016):883-891. |
入库方式： OAI收割
来源：高能物理研究所
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