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Structure and mechanism of CTP:phosphocholine cytidylyltransferase (LicC) from Streptococcus pneumoniae.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 Feb 08; Vol. 277 (6), pp. 4343-50. Date of Electronic Publication: 2001 Nov 12. - Publication Year :
- 2002
-
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.
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11706035
- Full Text :
- https://doi.org/10.1074/jbc.M109163200