1TD7

Interactions of a specific non-steroidal anti-inflammatory drug (NSAID) with group I phospholipase A2 (PLA2): Crystal structure of the complex formed between PLA2 and niflumic acid at 2.5 A resolution

1TD7 の概要

• エントリーDOI: 10.2210/pdb1td7/pdb
• 関連するPDBエントリー: 1MF4
• 分子名称: Phospholipase A2 isoform 3, CALCIUM ION, 2-{[3-(TRIFLUOROMETHYL)PHENYL]AMINO}NICOTINIC ACID, ... (4 entities in total)
• 機能のキーワード: phospholipase a2, enzyme, inhibitor, hydrolase
• 由来する生物種: Naja sagittifera
• 細胞内の位置: Secreted: P60045
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13505.89

構造登録者

Jabeen, T.,Singh, N.,Singh, R.K.,Sharma, S.,Perbandt, M.,Betzel, C.,Singh, T.P. (登録日: 2004-05-21, 公開日: 2004-06-08, 最終更新日: 2024-10-23)

主引用文献

Jabeen, T.,Singh, N.,Singh, R.K.,Sharma, S.,Somvanshi, R.K.,Dey, S.,Singh, T.P.
Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2: structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms resolution.
Acta Crystallogr.,Sect.D, 61:1579-1586, 2005

PubMed Abstract: Phospholipase A(2) (PLA(2); EC 3.1.3.4) catalyzes the first step of the production of proinflammatory compounds collectively known as eicosanoids. The binding of phospholipid substrates to PLA(2) occurs through a well formed hydrophobic channel. Surface plasmon resonance studies have shown that niflumic acid binds to Naja naja sagittifera PLA(2) with an affinity that corresponds to a dissociation constant (K(d)) of 4.3 x 10(-5) M. Binding studies of PLA(2) with niflumic acid were also carried out using a standard PLA(2) kit that gave an approximate binding constant, K(i), of 1.26 +/- 0.05 x 10(-6) M. Therefore, in order to establish the viability of PLA(2) as a potential target molecule for drug design against inflammation, arthritis and rheumatism, the three-dimensional structure of the complex of PLA(2) with the known anti-inflammatory agent niflumic acid [2-[3-(trifluoromethyl)anilino]nicotinic acid] has been determined at 2.5 Angstroms resolution. The structure of the complex has been refined to an R factor of 0.187. The structure determination reveals the presence of one niflumic acid molecule at the substrate-binding site of PLA(2). It shows that niflumic acid interacts with the important active-site residues His48 and Asp49 through two water molecules. It is observed that the niflumic acid molecule is completely buried in the substrate-binding hydrophobic channel. The conformations of the binding site in PLA(2) as well as that of niflumic acid are not altered upon binding. However, the orientation of the side chain of Trp19, which is located at the entry of the substrate-binding site, has changed from that found in the native PLA(2), indicating its familiar role.

PubMed: 16301791
DOI: 10.1107/S0907444905029604

実験手法

X-RAY DIFFRACTION (2.5 Å)