Human Serum Albumin Complexed with Myristate and AZT

Journal Article · Mon Jun 16 04:00:00 EDT 2008 · J. Struct. Biol.

DOI:https://doi.org/10.1016/j.jsb.2007.12.004· OSTI ID:1006632

Zhu, Lili; Yang, Feng; Chen, Liqing; Meehan, Edward J; Huang, Mingdong ^[1]

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1. UGA

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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1006632
• Journal Information: J. Struct. Biol., Journal Name: J. Struct. Biol. Journal Issue: (1) ; 04, 2008 Vol. 162; ISSN JSBIEM; ISSN 1047-8477
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

60 APPLIED LIFE SCIENCES
ALBUMINS
BLOOD SERUM
CARBOXYLIC ACIDS
COMPETITION
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
DISTRIBUTION
DRUGS
HUMAN POPULATIONS
INFORMATION
INTERACTIONS
THERAPY