title: Mechanism of the allosteric regulation of Streptococcus mutans 2'-deoxycytidylate deaminase.
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 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.
authors.affiliation: Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Disease, Chongqing Medical University, YiXueYuanlu-1, Chongqing, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Disease, Chongqing Medical University, YiXueYuanlu-1, Chongqing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Disease, Chongqing Medical University, YiXueYuanlu-1, Chongqing, People's Republic of China.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Gao
authors.affiliation: National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Science, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Su
authors.affiliation: Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Hou
authors.affiliation: Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000494:Allosteric Regulation; D018360:Crystallography, X-Ray; D003844:DCMP Deaminase / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D013295:Streptococcus mutans / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D013379:Substrate Specificity; D013942:Thymine Nucleotides / Q000378:metabolism
chemical_list: D013942:Thymine Nucleotides; D003844:DCMP Deaminase; C024157:thymidine 5'-triphosphate
keywords: 2′-deoxycytidylate deaminase; Streptococcus mutans; allosteric regulation; crystal structure; enzyme inactivation; enzyme mechanism; enzyme structure