3b9l: Difference between revisions

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[[Image:3b9l.jpg|left|200px]]
{{Seed}}
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{{STRUCTURE_3b9l|  PDB=3b9l  |  SCENE=  }}  
{{STRUCTURE_3b9l|  PDB=3b9l  |  SCENE=  }}  


'''Human serum albumin complexed with myristate and AZT'''
===Human serum albumin complexed with myristate and AZT===




==Overview==
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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.
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{{ABSTRACT_PUBMED_18258455}}


==About this Structure==
==About this Structure==
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==Reference==
==Reference==
A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography., Zhu L, Yang F, Chen L, Meehan EJ, Huang M, J Struct Biol. 2008 Apr;162(1):40-9. Epub 2007 Dec 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18258455 18258455]
A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography., Zhu L, Yang F, Chen L, Meehan EJ, Huang M, J Struct Biol. 2008 Apr;162(1):40-9. Epub 2007 Dec 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18258455 18258455]
Atomic structure and chemistry of human serum albumin., He XM, Carter DC, Nature. 1992 Jul 16;358(6383):209-15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1630489 1630489]
Structural basis of the drug-binding specificity of human serum albumin., Ghuman J, Zunszain PA, Petitpas I, Bhattacharya AA, Otagiri M, Curry S, J Mol Biol. 2005 Oct 14;353(1):38-52. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16169013 16169013]
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:[http://www.ncbi.nlm.nih.gov/pubmed/17067818 17067818]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Protein-ligands complex]]
[[Category: Protein-ligands complex]]
[[Category: Secreted]]
[[Category: Secreted]]
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