4X91

Crystal structure of Lysosomal Phospholipase A2 in complex with Isopropyl dodec-11-enylfluorophosphonate (IDFP)

4X91 の概要

• エントリーDOI: 10.2210/pdb4x91/pdb
• 関連するPDBエントリー: 4X90 4X92 4X93 4X94 4X95 4X96 4X97
• 分子名称: Group XV phospholipase A2, 2-acetamido-2-deoxy-beta-D-glucopyranose, propan-2-yl (R)-dodec-11-en-1-ylphosphonofluoridate, ... (7 entities in total)
• 機能のキーワード: hydrolase, phospholipase, idfp, acyltransferase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 179923.06

構造登録者

Glukhova, A.,Tesmer, J.J.G. (登録日: 2014-12-11, 公開日: 2015-03-11, 最終更新日: 2024-10-16)

主引用文献

Glukhova, A.,Hinkovska-Galcheva, V.,Kelly, R.,Abe, A.,Shayman, J.A.,Tesmer, J.J.
Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase.
Nat Commun, 6:6250-6250, 2015

PubMed Abstract: Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

PubMed: 25727495
DOI: 10.1038/ncomms7250

実験手法

X-RAY DIFFRACTION (2.3 Å)