5C2O

Crystal structure of Streptococcus mutans Deoxycytidylate Deaminase complexed with dTTP

Summary for 5C2O

• Entry DOI: 10.2210/pdb5c2o/pdb
• Descriptor: Putative deoxycytidylate deaminase, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: dcmp deaminase, inhibitor, allosteric regulation, enzyme complex, hydrolase
• Biological source: Streptococcus mutans
• Total number of polymer chains: 2
• Total formula weight: 42102.93

Authors

Li, Y.H.,Gao, Z.Q.,Hou, H.F.,Dong, Y.H. (deposition date: 2015-06-16, release date: 2016-07-13, Last modification date: 2024-03-20)

Primary citation

Li, Y.,Guo, Z.,Jin, L.,Wang, D.,Gao, Z.,Su, X.,Hou, H.,Dong, Y.
Mechanism of the allosteric regulation of Streptococcus mutans 2'-deoxycytidylate deaminase.
Acta Crystallogr D Struct Biol, 72:883-891, 2016

PubMed 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.

PubMed: 27377385
DOI: 10.1107/S2059798316009153

Experimental method

X-RAY DIFFRACTION (2.35 Å)