4ZCT

Crystal structure of the C-terminal catalytic domain of Plasmodium falciparum CTP:phosphocholine cytidylyltransferase

4ZCT の概要

• エントリーDOI: 10.2210/pdb4zct/pdb
• 関連するPDBエントリー: 4ZCP 4ZCQ 4ZCR 4ZCS
• 分子名称: Cholinephosphate cytidylyltransferase (2 entities in total)
• 機能のキーワード: transferase, malaria, cytidylyltransferase, phosphatidylcholine
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20810.12

構造登録者

Guca, E.,Hoh, F.,Guichou, J.-F.,Cerdan, R. (登録日: 2015-04-16, 公開日: 2016-09-14, 最終更新日: 2024-01-10)

主引用文献

Guca, E.,Nagy, G.N.,Hajdu, F.,Marton, L.,Izrael, R.,Hoh, F.,Yang, Y.,Vial, H.,Vertessy, B.G.,Guichou, J.F.,Cerdan, R.
Structural determinants of the catalytic mechanism of Plasmodium CCT, a key enzyme of malaria lipid biosynthesis.
Sci Rep, 8:11215-11215, 2018

PubMed 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.

PubMed: 30046154
DOI: 10.1038/s41598-018-29500-9

実験手法

X-RAY DIFFRACTION (2.22 Å)