Journal:IUCrJ:S2052252522006820
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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. | 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 (cartoon shown in gray) with the following complexes: | + | Superposition of structure of the HSA-ketoprofen complex (PDB ID: [[7jwn]]; cartoon shown in gray) with the following complexes: |
*<scene name='94/949060/Cv/11'>ESA-ketoprofen</scene> (PDB ID: [[6u4r]]). | *<scene name='94/949060/Cv/11'>ESA-ketoprofen</scene> (PDB ID: [[6u4r]]). | ||
*<scene name='94/949060/Cv/13'>BSA-ketoprofen</scene> (PDB ID: [[6qs9]]). | *<scene name='94/949060/Cv/13'>BSA-ketoprofen</scene> (PDB ID: [[6qs9]]). | ||
| - | *<scene name='94/949060/Cv/14'>LSA-ketoprofen</scene> (PDB ID: [[6ock]]). | + | *<scene name='94/949060/Cv/14'>LSA-ketoprofen</scene> (PDB ID: [[6ock]]). |
| + | *<scene name='94/949060/Cv/15'>HSA-ligand free</scene> (PDB ID: [[4k2c]]). | ||
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. 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. | 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. 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. | ||
Revision as of 11:55, 2 February 2023
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