Organism specific differences in binding of ketoprofen to serum albumin
Abstract
Serum albumin is a circulatory transport protein that has a highly conserved sequence and structure across mammalian organisms. Its ligand-binding properties are of importance as albumin regulates the pharmacokinetics of many drugs. Due to the high degree of structural conservation between mammalian albumins, nonhuman albumins such as bovine serum albumin or animal models are often used to understand human albumin–drug interactions. Ketoprofen is a popular nonsteroidal anti-inflammatory drug that is transported by albumin. Here, it is revealed that ketoprofen exhibits different binding-site preferences when interacting with human serum albumin compared with other mammalian albumins, despite the conservation of binding sites across species. The reasons for the observed differences were explored, including identifying ketoprofen binding determinants at specific sites and the influence of fatty acids and other ligands on drug binding. The presented results reveal that the drug-binding properties of albumins cannot easily be predicted based only on a complex of albumin from another organism and the conservation of drug sites between species. This work shows that understanding organism-dependent differences is essential for assessing the suitability of particular albumins for structural or biochemical studies.
Citation
Czub , M , Stewart , A J , Shabalin , I G & Minor , W 2022 , ' Organism specific differences in binding of ketoprofen to serum albumin ' , International Union of Crystallography Journal (IUCrJ) , vol. 9 , no. 5 , pp. 551-561 . https://doi.org/10.1107/S2052252522006820
Publication
International Union of Crystallography Journal (IUCrJ)
Status
Peer reviewed
ISSN
2052-2525Type
Journal article
Description
Funding: This work was supported by the National Institute of General Medical Sciences grants R01-GM132595, and federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States Department of Health and Human Services under contracts HHSN272201200026C and HHSN272201700060C. M.P.C. acknowledges the support of the Robert R. Wagner Fellowship at the University of Virginia. Results shown in this report are derived from work performed at Argonne National Laboratory (ANL), Structural Biology Center (SBC) at the Advanced Photon Source (APS), under U.S. Department of Energy, Office of Biological and Environmental Research contract DE-AC02-06CH11357. Declaration of Interests: One of the authors (W.M.) notes that he has also been involved in the development of state-of-the-art software, data management, and mining tools; some of them were commercialized by HKL Research and are mentioned in the paper. W.M. is the co-founder of HKL Research and a member of the board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Accession Codes: Coordinates and structure factors for the albumin-ketoprofen complex described in this paper have been deposited in the RCSB PDB with the following accession code: 7JWN. The authors have released the atomic coordinates and experimental data prior to the submission of the article.Collections
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