6OCJ

Crystal Structure of Equine Serum Albumin in Complex with Suprofen

6OCJ の概要

• エントリーDOI: 10.2210/pdb6ocj/pdb
• 分子名称: Serum albumin, (2S)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid, MALONATE ION, ... (6 entities in total)
• 機能のキーワード: helical, three-domain protein, serum albumin, transport protein
• 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: 66165.35

構造登録者

Sekula, B.,Zielinski, K.,Bujacz, A.,Bujacz, G. (登録日: 2019-03-24, 公開日: 2020-01-15, 最終更新日: 2024-10-16)

主引用文献

Zielinski, K.,Sekula, B.,Bujacz, A.,Szymczak, I.
Structural investigations of stereoselective profen binding by equine and leporine serum albumins.
Chirality, 32:334-344, 2020

PubMed Abstract: Serum albumin, the most abundant transport protein of mammalian blood, interacts with various nonsteroidal anti-inflammatory drugs (NSAIDs) affecting their disposition, metabolism, and excretion. A big group of chiral NSAIDs transported by albumin, profens, is created by derivatives of 2-arylpropionic acid. The chiral center in the structures of profens is adjacent to the carboxylate moiety and often determines different pharmacological properties of profen enantiomers. This study describes crystal structures of two albumins, isolated from equine and leporine serum, in complexes with three profens: ibuprofen, ketoprofen, and suprofen. Based on three-dimensional structures, the stereoselectivity of albumin is discussed and referred to the previously published albumin complexes with drugs. Drug Site 2 (DS2) of albumin, the bulky hydrophobic pocket of subdomain IIIA with a patch of polar residues, preferentially binds (S)-enantiomers of all investigated profens. Almost identical binding mode of all these drugs clearly indicates the stereoselectivity of DS2 towards (S)-profens in different albumin species. Also, the affinity studies show that DS2 is the major site that presents high affinity towards investigated drugs. Additionally, crystallographic data reveal the secondary binding sites of ketoprofen in leporine serum albumin and ibuprofen in equine serum albumin, both overlapping with previously identified naproxen binding sites: the cleft formed between subdomains IIIA and IIIB close to the fatty acid binding site 5 and the niche created between subdomains IIA and IIIA, called fatty acid site 6.

PubMed: 31905261
DOI: 10.1002/chir.23162

実験手法

X-RAY DIFFRACTION (2.5 Å)