6CI6

Crystal structure of equine serum albumin in complex with nabumetone

Summary for 6CI6

• Entry DOI: 10.2210/pdb6ci6/pdb
• Related: 3V08 5DQF 5V0V
• Descriptor: Serum albumin, SULFATE ION, nabumetone, ... (7 entities in total)
• Functional Keywords: structural genomics, center for structural genomics of infectious diseases, csgid, serum albumin, equine, nabumetone, transport protein
• Biological source: Equus caballus (Horse)
• Total number of polymer chains: 1
• Total formula weight: 67071.47

Authors

Venkataramany, B.S.,Czub, M.P.,Shabalin, I.G.,Handing, K.B.,Steen, E.H.,Cooper, D.R.,Joachimiak, A.,Satchell, K.J.F.,Minor, W.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2018-02-23, release date: 2018-03-07, Last modification date: 2024-10-16)

Primary citation

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., 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

Experimental method

X-RAY DIFFRACTION (2.8 Å)