4ZBR
Crystal Structure of Equine Serum Albumin in complex with Diclofenac and Naproxen
Summary for 4ZBR
| Entry DOI | 10.2210/pdb4zbr/pdb |
| Related | 4F5T 4F5U 4J2V 4OT2 |
| Descriptor | Serum albumin, 2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC ACID, (2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid, ... (9 entities in total) |
| Functional Keywords | helical, three-domain protein, serum albumin, transport protein, drugs delivery, diclofenac, naproxen |
| Biological source | Equus caballus (Horse) |
| Total number of polymer chains | 1 |
| Total formula weight | 67080.98 |
| Authors | Sekula, B.,Bujacz, A.,Bujacz, G. (deposition date: 2015-04-15, release date: 2015-12-23, Last modification date: 2024-11-20) |
| Primary citation | 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 Cited by 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: 26652101DOI: 10.1021/acs.jmedchem.5b00909 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.19 Å) |
Structure validation
Download full validation report
