Mechanism of the allosteric regulation ofStreptococcus mutans2′-deoxycytidylate deaminase
| Autor: | Li Jin, Yanhua Li, Yuhui Dong, Xiao-Dong Su, Zengqiang Gao, Zhen Guo, Haifeng Hou, Deqiang Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Protein Conformation viruses Allosteric regulation Plasma protein binding Crystallography X-Ray Substrate Specificity Streptococcus mutans Bacteriophage 03 medical and health sciences Protein structure Allosteric Regulation Structural Biology Hydrolase Thymine Nucleotides heterocyclic compounds DCMP Deaminase 030102 biochemistry & molecular biology biology Chemistry biology.organism_classification Enzyme structure Molecular Docking Simulation dCMP deaminase 030104 developmental biology Biochemistry Deoxycytidylate Deaminase |
| Zdroj: | Acta Crystallographica Section D Structural Biology. 72:883-891 |
| ISSN: | 2059-7983 |
| DOI: | 10.1107/s2059798316009153 |
| Popis: | 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 ofStreptococcus mutansdCD (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. |
| Databáze: | OpenAIRE |
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