Journal:IUCrJ:S2052252522006820
From Proteopedia
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Serum albumin (SA) is the most abundant plasma protein and a transporter of hormones, metal ions, and common metabolites, such as fatty acids and sugars, in the blood<ref name='Doweiko'>doi: 10.1177/0148607191015002207</ref><ref name='Peters'>Peters TJT. All About Albumin: Biochemistry, Genetics, and Medical Applications. 1st ed. Academic Press; 1995 http://linkinghub.elsevier.com/retrieve/pii/B9780125521109X50004</ref>. Thanks to its highly flexible structure, and the presence of several binding sites that are able to accommodate a variety of small molecules, SA is also the major facilitator of vascular drug transport. Up to now, ten binding sites within albumin have been characterized as drug sites, and nine of these have been demonstrated to bind at least three FDA-approved drugs<ref name='Handing'>doi: 10.1021/acs.jmedchem.0c00225</ref>. Due to the high degree of structural conservation between mammalian albumins, non-human albumins, such as bovine serum albumin, or animal models, are often used to understand human albumin-drug interactions. | Serum albumin (SA) is the most abundant plasma protein and a transporter of hormones, metal ions, and common metabolites, such as fatty acids and sugars, in the blood<ref name='Doweiko'>doi: 10.1177/0148607191015002207</ref><ref name='Peters'>Peters TJT. All About Albumin: Biochemistry, Genetics, and Medical Applications. 1st ed. Academic Press; 1995 http://linkinghub.elsevier.com/retrieve/pii/B9780125521109X50004</ref>. Thanks to its highly flexible structure, and the presence of several binding sites that are able to accommodate a variety of small molecules, SA is also the major facilitator of vascular drug transport. Up to now, ten binding sites within albumin have been characterized as drug sites, and nine of these have been demonstrated to bind at least three FDA-approved drugs<ref name='Handing'>doi: 10.1021/acs.jmedchem.0c00225</ref>. Due to the high degree of structural conservation between mammalian albumins, non-human albumins, such as bovine serum albumin, or animal models, are often used to understand human albumin-drug interactions. | ||
| - | <scene name='94/949060/Cv/4'>The overall structure of | + | 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. |
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| + | <scene name='94/949060/Cv/4'>The overall structure of Human SA complex with ketoprofen</scene>. <span class="bg-yellow"><span class="far fa-hand-point-right"></span> Remember to drag the structures with the mouse to rotate them.</span> 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]]): | Ketoprofen binding sites in HSA (PDB ID: [[7jwn]]): | ||
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*<scene name='94/949060/Cv/16'>HSA-myristic acid</scene> (PDB ID: [[1bj5]]). | *<scene name='94/949060/Cv/16'>HSA-myristic acid</scene> (PDB ID: [[1bj5]]). | ||
| - | + | 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. | |
<b>References</b><br> | <b>References</b><br> | ||
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