1JYL

Catalytic Mechanism of CTP:phosphocholine Cytidylyltransferase from Streptococcus pneumoniae (LicC)

Summary for 1JYL

• Entry DOI: 10.2210/pdb1jyl/pdb
• Related: 1JYK
• Descriptor: CTP:phosphocholine Cytidylyltransferase, MAGNESIUM ION, [2-CYTIDYLATE-O'-PHOSPHONYLOXYL]-ETHYL-TRIMETHYL-AMMONIUM, ... (4 entities in total)
• Functional Keywords: licc, 3d structure, ctp:phosphocholine cytidylyltransferase, transferase
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 4
• Total formula weight: 120896.74

Authors

Kwak, B.-Y.,Yun, M.,Park, H.-w. (deposition date: 2001-09-12, release date: 2002-02-22, Last modification date: 2024-02-07)

Primary citation

Kwak, B.Y.,Zhang, Y.M.,Yun, M.,Heath, R.J.,Rock, C.O.,Jackowski, S.,Park, H.W.
Structure and mechanism of CTP:phosphocholine cytidylyltransferase (LicC) from Streptococcus pneumoniae.
J.Biol.Chem., 277:4343-4350, 2002

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.

PubMed: 11706035
DOI: 10.1074/jbc.M109163200

Experimental method

X-RAY DIFFRACTION (2.4 Å)