Journal:IUCrJ:S2052252522006820
From Proteopedia
Organism Specific Differences in Binding of Ketoprofen to Serum AlbuminMateusz P. Czub, Alan J. Stewart, Ivan G. Shabalin, and Wladek Minor [1] Molecular Tour The results reported herein provide insight into the circulatory transport of ketoprofen, a popular nonsteroidal anti-inflammatory drug (NSAID), across species. The structure of the ketoprofen complex with human SA revealed that four ketoprofen molecules bind to three distinct sites within SA, which only partially overlap with sites previously reported to bind ketoprofen in SAs from other species. . Remember to drag the structures with the mouse to rotate them. Albumin subdomains are each shown in a different color. Roman numerals (I, II, III) are associated with domains and letters (e.g., IB) with subdomains. Ketoprofen molecules are shown with atoms in white spheres. Ketoprofen binding sites in HSA (PDB ID: 7jwn):
in HSA (PDB ID: 7jwn) and LSA (PDB ID: 6ock). (S)-Ketoprofen molecule and molecule of a fatty acid bound to HSA are shown in stick representation with oxygen atoms in red and carbon atoms in yellow, while a molecule of (S)-ketoprofen bound to LSA is shown in stick representation with oxygen atoms in red and carbon atoms in gray. Superposition of structure of the HSA-ketoprofen complex (PDB ID: 7jwn; cartoon shown in gray) with the following complexes: We explored the reasons for the observed differences, including identifying residues and interactions required for ketoprofen binding at specific sites and the influence of metabolites and components of crystallization solution on drug binding. The presented results reveal that the drug-binding properties of albumins cannot be easily 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. References
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