3B9L

Human serum albumin complexed with myristate and AZT

Summary for 3B9L

• Entry DOI: 10.2210/pdb3b9l/pdb
• Related: 3B9M
• Descriptor: Serum albumin, MYRISTIC ACID, 3'-azido-3'-deoxythymidine (3 entities in total)
• Functional Keywords: protein-ligands complex, cleavage on pair of basic residues, disease mutation, glycation, glycoprotein, lipid-binding, metal-binding, secreted, lipid binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P02768
• Total number of polymer chains: 1
• Total formula weight: 68704.30

Authors

Zhu, L.,Yang, F.,Chen, L.,Meehan, E.J.,Huang, M. (deposition date: 2007-11-05, release date: 2008-05-27, Last modification date: 2024-11-06)

Primary citation

Zhu, L.,Yang, F.,Chen, L.,Meehan, E.J.,Huang, M.
A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography
J.Struct.Biol., 162:40-49, 2008

PubMed Abstract: 3'-Azido-3'-deoxythymidine (AZT) is the first clinically effective drug for the treatment of human immunodeficiency virus infection. The drug interaction with human serum albumin (HSA) has been an important component in understanding its mechanism of action, especially in drug distribution and in drug-drug interaction on HSA in the case of multi-drug therapy. We present here crystal structures of a ternary HSA-Myr-AZT complex and a quaternary HSA-Myr-AZT-SAL complex (Myr, myristate; SAL, salicylic acid). From this study, a new drug binding subsite on HSA Sudlow site 1 was identified. The presence of fatty acid is needed for the creation of this subsite due to fatty acid induced conformational changes of HSA. Thus, the Sudlow site 1 of HSA can be divided into three non-overlapped subsites: a SAL subsite, an indomethacin subsite and an AZT subsite. Binding of a drug to HSA often influences simultaneous binding of other drugs. From the HSA-Myr-AZT-SAL complex structure, we observed the coexistence of two drugs (AZT and SAL) in Sudlow site 1 and the competition between these two drugs in subdomain IB. These results provide new structural information on HSA-drug interaction and drug-drug interaction on HSA.

PubMed: 18258455
DOI: 10.1016/j.jsb.2007.12.004

Experimental method

X-RAY DIFFRACTION (2.6 Å)