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Organism-specific differences in the binding of ketoprofen to serum albumin

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...

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Autores principales: Czub, Mateusz P., Stewart, Alan J., Shabalin, Ivan G., Minor, Wladek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438504/
https://www.ncbi.nlm.nih.gov/pubmed/36071810
http://dx.doi.org/10.1107/S2052252522006820
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author Czub, Mateusz P.
Stewart, Alan J.
Shabalin, Ivan G.
Minor, Wladek
author_facet Czub, Mateusz P.
Stewart, Alan J.
Shabalin, Ivan G.
Minor, Wladek
author_sort Czub, Mateusz P.
collection PubMed
description 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.
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spelling pubmed-94385042022-09-06 Organism-specific differences in the binding of ketoprofen to serum albumin Czub, Mateusz P. Stewart, Alan J. Shabalin, Ivan G. Minor, Wladek IUCrJ Research Papers 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. International Union of Crystallography 2022-07-16 /pmc/articles/PMC9438504/ /pubmed/36071810 http://dx.doi.org/10.1107/S2052252522006820 Text en © Mateusz P. Czub et al. 2022 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
spellingShingle Research Papers
Czub, Mateusz P.
Stewart, Alan J.
Shabalin, Ivan G.
Minor, Wladek
Organism-specific differences in the binding of ketoprofen to serum albumin
title Organism-specific differences in the binding of ketoprofen to serum albumin
title_full Organism-specific differences in the binding of ketoprofen to serum albumin
title_fullStr Organism-specific differences in the binding of ketoprofen to serum albumin
title_full_unstemmed Organism-specific differences in the binding of ketoprofen to serum albumin
title_short Organism-specific differences in the binding of ketoprofen to serum albumin
title_sort organism-specific differences in the binding of ketoprofen to serum albumin
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438504/
https://www.ncbi.nlm.nih.gov/pubmed/36071810
http://dx.doi.org/10.1107/S2052252522006820
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