6U4X
Crystal structure of Equine Serum Albumin complex with ibuprofen
Summary for 6U4X
| Entry DOI | 10.2210/pdb6u4x/pdb |
| Descriptor | Serum albumin, UNKNOWN LIGAND, UNKNOWN ATOM OR ION, ... (6 entities in total) |
| Functional Keywords | albumin, ibuprofen, nsaid, sa, esa, center for structural genomics of infectious diseases, csgid, transport protein |
| Biological source | Equus caballus (Horse) |
| Total number of polymer chains | 1 |
| Total formula weight | 67141.28 |
| Authors | 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) (deposition date: 2019-08-26, release date: 2019-09-04, 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., 63:6847-6862, 2020 Cited by 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: 32469516DOI: 10.1021/acs.jmedchem.0c00225 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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