2I2Z

Human serum albumin complexed with myristate and aspirin

Summary for 2I2Z

• Entry DOI: 10.2210/pdb2i2z/pdb
• Related: 2BXL 2I30
• Descriptor: Serum albumin, MYRISTIC ACID, 2-HYDROXYBENZOIC ACID (3 entities in total)
• Functional Keywords: plasma protein, metal-binding, lipid-binding, lipid binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02768
• Total number of polymer chains: 1
• Total formula weight: 67892.23

Authors

Yang, F.,Bian, C.,Zhu, L.,Zhao, G.,Huang, Z.,Huang, M. (deposition date: 2006-08-17, release date: 2006-12-12, Last modification date: 2024-11-20)

Primary citation

Yang, F.,Bian, C.,Zhu, L.,Zhao, G.,Huang, Z.,Huang, M.
Effect of human serum albumin on drug metabolism: Structural evidence of esterase activity of human serum albumin
J.Struct.Biol., 157:348-355, 2007

PubMed Abstract: Human 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.

PubMed: 17067818
DOI: 10.1016/j.jsb.2006.08.015

Experimental method

X-RAY DIFFRACTION (2.7 Å)