| Title | Mechanism of the allosteric regulation of Streptococcus mutans 2 '-deoxycytidylate deaminase |
| Authors | Li, Yanhua Guo, Zhen Jin, Li Wang, Deqiang Gao, Zengqiang Su, Xiaodong Hou, Haifeng Dong, Yuhui |
| Affiliation | Chinese Acad Sci, Beijing Synchrotron Radiat Facil, Inst High Energy Phys, Beijing 100049, Peoples R China. Chongqing Med Univ, Key Lab Mol Biol Infect Dis, YiXueYuanlu 1, Chongqing, Peoples R China. Chongqing Med Univ, Coll Lab Med, YiXueYuanlu 1, Chongqing, Peoples R China. Peking Univ, Coll Life Sci, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China. |
| Keywords | allosteric regulation crystal structure enzyme inactivation enzyme mechanism enzyme structure 2 '-deoxycytidylate deaminase Streptococcus mutans HUMAN DEOXYCYTIDYLATE DEAMINASE HEPATITIS-B-VIRUS CYTIDINE DEAMINASE CRYSTAL-STRUCTURE DNTP POOLS SUBSTRATE INHIBITOR SUBUNIT COMPLEX BINDING |
| Issue Date | 2016 |
| Publisher | ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY |
| Citation | ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY.2016,72(7),883-891. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/492028 |
| ISSN | 2059-7983 |
| DOI | 10.1107/S2059798316009153 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生命科学学院 蛋白质与植物基因研究国家重点实验室 |
