3B9M

Human serum albumin complexed with myristate, 3'-azido-3'-deoxythymidine (AZT) and salicylic acid

3B9M の概要

• エントリーDOI: 10.2210/pdb3b9m/pdb
• 関連するPDBエントリー: 3B9L
• 分子名称: Serum albumin, MYRISTIC ACID, 3'-azido-3'-deoxythymidine, ... (4 entities in total)
• 機能のキーワード: protein-ligands complex, cleavage on pair of basic residues, disease mutation, glycation, glycoprotein, lipid-binding, metal-binding, secreted, lipid binding protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted: P02768
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68484.93

構造登録者

Zhu, L.,Yang, F.,Chen, L.,Meehan, E.J.,Huang, M. (登録日: 2007-11-05, 公開日: 2008-05-27, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)