8PC4

MEMBRANE TARGET COMPLEX 1

8PC4 の概要

• エントリーDOI: 10.2210/pdb8pc4/pdb
• 分子名称: N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D, ZINC ION, 1,2-Distearoyl-sn-glycerophosphoethanolamine, ... (6 entities in total)
• 機能のキーワード: membrane, target, dimer, drug, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97290.01

構造登録者

Garau, G. (登録日: 2023-06-09, 公開日: 2024-06-26, 最終更新日: 2025-04-02)

主引用文献

Chiarugi, S.,Margheriti, F.,De Lorenzi, V.,Martino, E.,Margheritis, E.G.,Moscardini, A.,Marotta, R.,Chaves-Sanjuan, A.,Del Seppia, C.,Federighi, G.,Lapi, D.,Bandiera, T.,Rapposelli, S.,Scuri, R.,Bolognesi, M.,Garau, G.
NAPE-PLD is target of thiazide diuretics.
Cell Chem Biol, 32:449-, 2025

PubMed Abstract: Thiazide and thiazide-like diuretics are among the most efficacious and used drugs for the treatment of hypertension, edema, and major cardiovascular outcomes. Despite more then than six decades of clinical use, the molecular target and mechanism of action by which these drugs cure hypertension after long-term use have remained mysterious. Here we report the discovery and validation of a previously unknown renal and extrarenal target of these antihypertensives, the membrane-associated phospholipase N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) of the endocannabinoid system. Structural and functional insights, together with preclinical studies in hypertensive rats, disclose the molecular and physiological basis by which thiazides cause acute diuresis and, at the same time, the distinctive chronic reduction of vascular resistance. Our results shed light on the mechanism of treatment of hypertension and will be useful for developing more efficacious medications for the management of vascular risk factors, as well as associated leukoencephalopathies and myelin disorders.

PubMed: 39999832
DOI: 10.1016/j.chembiol.2025.01.008

実験手法

X-RAY DIFFRACTION (2.85 Å)