Structure and mechanism of CTP:phosphocholine cytidylyltransferase (LicC) from Streptococcus pneumoniae.

Article Details

Citation

Copy to clipboard

Kwak BY, Zhang YM, Yun M, Heath RJ, Rock CO, Jackowski S, Park HW

Structure and mechanism of CTP:phosphocholine cytidylyltransferase (LicC) from Streptococcus pneumoniae.

J Biol Chem. 2002 Feb 8;277(6):4343-50. Epub 2001 Nov 12.

PubMed ID

11706035 [ View in PubMed

]

Abstract

Pneumococcal 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.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
LicC protein	A0A0H2UQB5	Details