7wkz
From Proteopedia
Crystal structure of the HSA complex with mycophenolate and aripiprazole
Structural highlights
DiseaseALBU_HUMAN Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:103600. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.[1] [2] [3] [4] FunctionALBU_HUMAN Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.[5] Publication Abstract from PubMedMycophenolic acid (MP) is an active metabolite of mycophenolate mofetil, a widely used immunosuppressive drug. MP normally exhibits high plasma protein binding (97-99%), but its binding rate is decreased in patients with renal insufficiency. This decreased protein binding is thought to be associated with leukopenia, a side effect of MP. In this study, we characterized the change in protein binding of MP in renal failure patients. Our findings indicate that MP binds strongly to subdomain IIA of human serum albumin. X-ray crystallographic data indicated that the isobenzofuran group of MP forms a stacking interaction with Trp214, and the carboxyl group of MP is located at a position that allows the formation of hydrogen bonds with Tyr150, His242, or Arg257. Due to the specific binding of MP to subdomain IIA, MP is thought to be displaced by uremic toxin (3-carboxy-4-methyl-5-propyl-2-furan-propionic acid) and fatty acids (oleate or myristate) that can bind to subdomain IIA, resulting in the decreased plasma protein binding of MP in renal failure. Structural Basis of the Change in the Interaction Between Mycophenolic Acid and Subdomain IIA of Human Serum Albumin During Renal Failure.,Yamasaki K, Teshima H, Yukizawa R, Kuyama K, Tsukigawa K, Nishi K, Otagiri M, Kawai A J Med Chem. 2023 Jan 12;66(1):951-961. doi: 10.1021/acs.jmedchem.2c01790. Epub , 2022 Dec 20. PMID:36538495[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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