2i2z
From Proteopedia
Human serum albumin complexed with myristate and aspirin
Structural highlights
Disease[ALBU_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] Function[ALBU_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] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman serum albumin (HSA) is the most abundant plasma protein in the human body with a plasma concentration of 0.6mM. HSA plays an important role in drug transport and metabolism. Enzymatic activity of HSA on different substrates or drugs has been studied and documented. The structural mechanism of this activity, however, is unknown. In this study, we have determined the crystal structures of HSA-myristate in a complex of aspirin and of salicylic acid, respectively. The crystal structure of HSA-myristate-aspirin illustrates that aspirin transfers acetyl group to Lys199 and is hydrolyzed into salicylic acid by HSA. The hydrolysis product, salicylic acid, remains bound to HSA at a similar location, but it shows a very different orientation when compared with the salicylic acid in the HSA-myristate-salicylic acid ternary complex. These results not only provide the structural evidence of esterase activity of HSA, and demonstrate the conformational plasticity of HSA on drug binding, but also may provide structural information for the modulation of HSA-drug interaction by computational approach based on HSA-drug structure. Effect of human serum albumin on drug metabolism: structural evidence of esterase activity of human serum albumin.,Yang F, Bian C, Zhu L, Zhao G, Huang Z, Huang M J Struct Biol. 2007 Feb;157(2):348-55. Epub 2006 Sep 9. PMID:17067818[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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