3H1X

Simultaneous inhibition of anti-coagulation and inflammation: Crystal structure of phospholipase A2 complexed with indomethacin at 1.4 A resolution reveals the presence of the new common ligand binding site

3H1X の概要

• エントリーDOI: 10.2210/pdb3h1x/pdb
• 関連するPDBエントリー: 1FB2
• 分子名称: Phospholipase A2 VRV-PL-VIIIa, INDOMETHACIN, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: pla2, anti-inflammatory, anti-coagulant, indomethacin, hydrolase
• 由来する生物種: Daboia russellii russellii (Indian Russell's viper)
• 細胞内の位置: Secreted: P59071
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14275.74

構造登録者

Singh, N.,Prem Kumar, R.,Sharma, S.,Kaur, P.,Singh, T.P. (登録日: 2009-04-14, 公開日: 2009-06-09, 最終更新日: 2024-11-13)

主引用文献

Singh, N.,Kumar, R.P.,Kumar, S.,Sharma, S.,Mir, R.,Kaur, P.,Srinivasan, A.,Singh, T.P.
Simultaneous inhibition of anti-coagulation and inflammation: crystal structure of phospholipase A2 complexed with indomethacin at 1.4 A resolution reveals the presence of the new common ligand-binding site
J.Mol.Recognit., 22:437-445, 2009

PubMed Abstract: A novel ligand-binding site with functional implications has been identified in phospholipase A(2) (PLA(2)). The binding of non-steroidal anti-inflammatory agent indomethacin at this site blocks both catalytic and anti-coagulant actions of PLA(2). A group IIA PLA(2) has been isolated from Daboia russelli pulchella (Russell's viper) which is enzymatically active as well as induces a strong anti-coagulant action. The binding studies have shown that indomethacin reduces the effects of both anti-coagulant and pro-inflammatory actions of PLA(2). A group IIA PLA(2) was co-crystallized with indomethacin and the structure of the complex has been determined at 1.4 A resolution. The structure determination has revealed the presence of an indomethacin molecule in the structure of PLA(2) at a site which is distinct from the conventional substrate-binding site. One of the carboxylic group oxygen atoms of indomethacin interacts with Asp 49 and His 48 through the catalytically important water molecule OW 18 while the second carboxylic oxygen atom forms an ionic interaction with the side chain of Lys 69. It is well known that the residues, His 48 and Asp 49 are essential for catalysis while Lys 69 is a part of the anti-coagulant loop (residues, 54-77). Indomethacin binds in such a manner that it blocks the access to both, it works as a dual inhibitor for catalytic and anti-coagulant actions of PLA(2). This new binding site in PLA(2) has been observed for the first time and indomethacin is the first compound that has been shown to bind at this novel site resulting in the prevention of anti-coagulation and inflammation.

PubMed: 19462410
DOI: 10.1002/jmr.960

実験手法

X-RAY DIFFRACTION (1.4 Å)