PDBsum entry 4zcp

Transferase

PDB id: 4zcp

Contents

Protein chain

129 a.a.

Ligands

C5P

Waters ×43

PDB id:

4zcp

Name:

Transferase

Title:

Crystal structure of thE C-terminal catalytic domain of plasmodium falciparum ctp:phosphocholine cytidylyltransferase in complex with cmp

Structure:

Cholinephosphate cytidylyltransferase. Chain: a. Engineered: yes

Source:

Plasmodium falciparum. Organism_taxid: 5833. Gene: ctp, mal13p1.86. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.98Å R-factor: 0.209 R-free: 0.247

Authors:

E.Guca,F.Hoh,J.-F.Guichou,R.Cerdan

Key ref:

E.Guca et al. (2018). Structural determinants of the catalytic mechanism of Plasmodium CCT, a key enzyme of malaria lipid biosynthesis. Sci Rep, 8, 11215. PubMed id: 30046154

Date:

16-Apr-15 Release date: 14-Sep-16

Protein chain

Q8IEE9  (Q8IEE9_PLAF7) -  choline-phosphate cytidylyltransferase from Plasmodium falciparum (isolate 3D7)

Seq: 896 a.a.

Struc: 129 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.7.15 - choline-phosphate cytidylyltransferase.
• Reaction: phosphocholine + CTP + H⁺ = CDP-choline + diphosphate

phosphocholine (Bound ligand (Het Group name = C5P) matches with 72.41% similarity) + CTP + H(+) = CDP-choline + diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Sci Rep 8:11215 (2018)

PubMed id: 30046154

Structural determinants of the catalytic mechanism of Plasmodium CCT, a key enzyme of malaria lipid biosynthesis.

E.Guca, G.N.Nagy, F.Hajdú, L.Marton, R.Izrael, F.Hoh, Y.Yang, H.Vial, B.G.Vértessy, J.F.Guichou, R.Cerdan.

ABSTRACT

The development of the malaria parasite, Plasmodium falciparum, in the human erythrocyte, relies on phospholipid metabolism to fulfil the massive need for membrane biogenesis. Phosphatidylcholine (PC) is the most abundant phospholipid in Plasmodium membranes. PC biosynthesis is mainly ensured by the de novo Kennedy pathway that is considered as an antimalarial drug target. The CTP:phosphocholine cytidylyltransferase (CCT) catalyses the rate-limiting step of the Kennedy pathway. Here we report a series of structural snapshots of the PfCCT catalytic domain in its free, substrate- and product-complexed states that demonstrate the conformational changes during the catalytic mechanism. Structural data show the ligand-dependent conformational variations of a flexible lysine. Combined kinetic and ligand-binding analyses confirm the catalytic roles of this lysine and of two threonine residues of the helix αE. Finally, we assessed the variations in active site residues between Plasmodium and mammalian CCT which could be exploited for future antimalarial drug design.