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Catalytic Mechanism of CTP:phosphocholine Cytidylyltransferase from Streptococcus pneumoniae (LicC)
Structural highlights
FunctionLICC_STRR6 Cytidylyltransferase involved in the biosynthesis of the phosphocholine containing cell wall constituents, teichoic acid and lipoteichoic acid, which are essential for cell separation and pathogenesis (PubMed:8837483). Catalyzes the activation of phosphocholine (P-Cho) to CDP-choline (CDP-Cho) (PubMed:11466299, PubMed:11706035, PubMed:11786295, PubMed:31420548, PubMed:8837483). Can also use phosphoethanolamine and 2-aminoethylphosphonate, with much lower efficiency (PubMed:11466299, PubMed:31420548). Shows lower activity with dCTP, weak activity with ATP and no activity with GTP, TTP, UTP, dATP, dGTP and dTTP (PubMed:11466299, PubMed:11786295).[1] [2] [3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPneumococcal LicC is a member of the nucleoside triphosphate transferase superfamily and catalyzes the transfer of a cytidine monophosphate from CTP to phosphocholine to form CDP-choline. The structures of apo-LicC and the LicC-CDP-choline-Mg(2+) ternary complex were determined, and the comparison of these structures reveals a significant conformational change driven by the multivalent coordination of Mg(2+). The key event is breaking the Glu(216)-Arg(129) salt bridge, which triggers the coalescence of four individual beta-strands into two extended beta-sheets. These movements reorient the side chains of Trp(136) and Tyr(190) for the optimal binding and alignment of the phosphocholine moiety. Consistent with these conformational changes, LicC operates via a compulsory ordered kinetic mechanism. The structures explain the substrate specificity of LicC for CTP and phosphocholine and implicate a direct role for Mg(2+) in aligning phosphocholine for in-line nucleophilic attack and stabilizing the negative charge that develops in the pentacoordinate transition state. These results provide a structural basis for assigning a specific role for magnesium in the catalytic mechanism of pneumococcal LicC. Structure and mechanism of CTP:phosphocholine cytidylyltransferase (LicC) from Streptococcus pneumoniae.,Kwak BY, Zhang YM, Yun M, Heath RJ, Rock CO, Jackowski S, Park HW J Biol Chem. 2002 Feb 8;277(6):4343-50. Epub 2001 Nov 12. PMID:11706035[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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