8UL9

Cholinephosphotransferase in complex with diacylglycerol

8UL9 の概要

• エントリーDOI: 10.2210/pdb8ul9/pdb
• EMDBエントリー: 42357
• 分子名称: Cholinephosphotransferase 1, MAGNESIUM ION, 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (5 entities in total)
• 機能のキーワード: lipid metabolism, phospholipid synthesis, membrane protein enzyme, choline metabolism, membrane protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94364.54

構造登録者

Roberts, J.R.,Maeda, S.,Ohi, M.D. (登録日: 2023-10-16, 公開日: 2024-10-23, 最終更新日: 2025-01-15)

主引用文献

Roberts, J.R.,Horibata, Y.,Kwarcinski, F.E.,Lam, V.,Raczkowski, A.M.,Hubbard, A.,White, B.,Sugimoto, H.,Tall, G.G.,Ohi, M.D.,Maeda, S.
Structural basis for catalysis and selectivity of phospholipid synthesis by eukaryotic choline-phosphotransferase.
Nat Commun, 16:111-111, 2025

PubMed Abstract: Phospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesized de novo through the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5'-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) that are the main phospholipids in eukaryotic cells. Here we present the structure of the yeast CPT1 in multiple substrate-bound states. Structural and functional analysis of these binding-sites reveal the critical residues for the DAG acyl-chain preference and the choline/ethanolamine selectivity. Additionally, we present the structure in complex with a potent inhibitor characterized in this study. The ensemble of structures allows us to propose the reaction mechanism for phospholipid biosynthesis by the family of CDP-alcohol phosphotransferases (CDP-APs).

PubMed: 39747155
DOI: 10.1038/s41467-024-55673-1

実験手法

ELECTRON MICROSCOPY (3.2 Å)