Mechanism of the allosteric regulation of Streptococcus mutans 2′‐deoxycytidylate deaminase. Issue 7 (5th July 2016)

• Record Type: Journal Article
• Authors: Li, Yanhua; Guo, Zhen; Jin, Li; Wang, Deqiang; Gao, Zengqiang; Su, Xiaodong; Hou, Haifeng; Dong, Yuhui
• Is Part Of: Acta crystallographica. Volume 72:Issue 7(2016)
• Page Start: 883
• Page End: 891
• Publication Date: 2016-07-05
• Subjects: allosteric regulation -- crystal structure -- enzyme inactivation -- enzyme mechanism -- enzyme structure -- 2′‐deoxycytidylate deaminase -- Streptococcus mutans; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798316009153
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : The allosteric regulation of S. mutans 2′‐deoxycytidylate deaminase by dCTP/dTTP is based on a concentration‐dependent competition mechanism. This is the first pair of dTTP/dCTP‐bound crystal structures of deoxycytidylate deaminase from the same species to be reported. 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.