4ZBR

Crystal Structure of Equine Serum Albumin in complex with Diclofenac and Naproxen

4ZBR の概要

• エントリーDOI: 10.2210/pdb4zbr/pdb
• 関連するPDBエントリー: 4F5T 4F5U 4J2V 4OT2
• 分子名称: Serum albumin, 2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC ACID, (2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid, ... (9 entities in total)
• 機能のキーワード: helical, three-domain protein, serum albumin, transport protein, drugs delivery, diclofenac, naproxen
• 由来する生物種: Equus caballus (Horse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 67080.98

構造登録者

Sekula, B.,Bujacz, A.,Bujacz, G. (登録日: 2015-04-15, 公開日: 2015-12-23, 最終更新日: 2024-11-20)

主引用文献

Sekula, B.,Bujacz, A.
Structural Insights into the Competitive Binding of Diclofenac and Naproxen by Equine Serum Albumin.
J.Med.Chem., 59:82-89, 2016

PubMed Abstract: The binding modes to equine serum albumin (ESA) of two nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac (Dic) and naproxen (Nps), were studied by X-ray crystallography and isothermal titration calorimetry. On the basis of the crystal structure of ESA/Dic determined to a resolution of 1.92 Å and the structure of the previously described ESA/Nps complex (2.42 Å), it was found that both NSAIDs bind within drug site 2 (DS2) of ESA and both occupy secondary binding sites in separate cavities of domain II (Nps) and domain III (Dic). The two structures of the ternary complex ESA/Dic/Nps, obtained by competitive cocrystallization (2.19 Å) and through a displacement experiment (2.35 Å), were determined to investigate possible competition of these widely used pharmaceutical drugs in binding to ESA. In these complexes Nps occupies the DS2 pocket common for both drugs, whereas the other distinct binding sites of Dic and Nps remain unaffected. These results suggest that combined application of both drugs may result in increased concentration of free diclofenac in plasma.

PubMed: 26652101
DOI: 10.1021/acs.jmedchem.5b00909

実験手法

X-RAY DIFFRACTION (2.19 Å)