6U4X

Crystal structure of Equine Serum Albumin complex with ibuprofen

6U4X の概要

• エントリーDOI: 10.2210/pdb6u4x/pdb
• 分子名称: Serum albumin, UNKNOWN LIGAND, UNKNOWN ATOM OR ION, ... (6 entities in total)
• 機能のキーワード: albumin, ibuprofen, nsaid, sa, esa, center for structural genomics of infectious diseases, csgid, 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: 67141.28

構造登録者

Czub, M.P.,Handing, K.B.,Venkataramany, B.S.,Steen, E.H.,Shabalin, I.G.,Satchell, K.J.,Joachimiak, A.,Minor, W.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2019-08-26, 公開日: 2019-09-04, 最終更新日: 2024-10-16)

主引用文献

Czub, M.P.,Handing, K.B.,Venkataramany, B.S.,Cooper, D.R.,Shabalin, I.G.,Minor, W.
Albumin-Based Transport of Nonsteroidal Anti-Inflammatory Drugs in Mammalian Blood Plasma.
J.Med.Chem., 63:6847-6862, 2020

PubMed Abstract: Every day, hundreds of millions of people worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs), often in conjunction with multiple other medications. In the bloodstream, NSAIDs are mostly bound to serum albumin (SA). We report the crystal structures of equine serum albumin complexed with four NSAIDs (ibuprofen, ketoprofen, etodolac, and nabumetone) and the active metabolite of nabumetone (6-methoxy-2-naphthylacetic acid, 6-MNA). These compounds bind to seven drug-binding sites on SA. These sites are generally well-conserved between equine and human SAs, but ibuprofen binds to both SAs in two drug-binding sites, only one of which is common. We also compare the binding of ketoprofen by equine SA to binding of it by bovine and leporine SAs. Our comparative analysis of known SA complexes with FDA-approved drugs clearly shows that multiple medications compete for the same binding sites, indicating possibilities for undesirable physiological effects caused by drug-drug displacement or competition with common metabolites. We discuss the consequences of NSAID binding to SA in a broader scientific and medical context, particularly regarding achieving desired therapeutic effects based on an individual's drug regimen.

PubMed: 32469516
DOI: 10.1021/acs.jmedchem.0c00225

実験手法

X-RAY DIFFRACTION (2.25 Å)