1ha2
From Proteopedia
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|PDB= 1ha2 |SIZE=350|CAPTION= <scene name='initialview01'>1ha2</scene>, resolution 2.50Å | |PDB= 1ha2 |SIZE=350|CAPTION= <scene name='initialview01'>1ha2</scene>, resolution 2.50Å | ||
|SITE= <scene name='pdbsite=WRS:Wrs+Binding+Site+For+Chain+A'>WRS</scene> | |SITE= <scene name='pdbsite=WRS:Wrs+Binding+Site+For+Chain+A'>WRS</scene> | ||
| - | |LIGAND= <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene> | + | |LIGAND= <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=WRS:4-HYDROXY-3-[(1S,3S)-3-HYDROXY-1-PHENYLBUTYL]-2H-CHROMEN-2-ONE'>WRS</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ha2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ha2 OCA], [http://www.ebi.ac.uk/pdbsum/1ha2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ha2 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Human serum albumin (HSA) is an abundant transport protein found in plasma that binds a wide variety of drugs in two primary binding sites (I and II) and can have a significant impact on their pharmacokinetics. We have determined the crystal structures at 2.5 A-resolution of HSA-myristate complexed with the R-(+) and S-(-) enantiomers of warfarin, a widely used anticoagulant that binds to the protein with high affinity. The structures confirm that warfarin binds to drug site I (in subdomain IIA) in the presence of fatty acids and reveal the molecular details of the protein-drug interaction. The two enantiomers of warfarin adopt very similar conformations when bound to the protein and make many of the same specific contacts with amino acid side chains at the binding site, thus accounting for the relative lack of stereospecificity of the HSA-warfarin interaction. The conformation of the warfarin binding pocket is significantly altered upon binding of fatty acids, and this can explain the observed enhancement of warfarin binding to HSA at low levels of fatty acid. | Human serum albumin (HSA) is an abundant transport protein found in plasma that binds a wide variety of drugs in two primary binding sites (I and II) and can have a significant impact on their pharmacokinetics. We have determined the crystal structures at 2.5 A-resolution of HSA-myristate complexed with the R-(+) and S-(-) enantiomers of warfarin, a widely used anticoagulant that binds to the protein with high affinity. The structures confirm that warfarin binds to drug site I (in subdomain IIA) in the presence of fatty acids and reveal the molecular details of the protein-drug interaction. The two enantiomers of warfarin adopt very similar conformations when bound to the protein and make many of the same specific contacts with amino acid side chains at the binding site, thus accounting for the relative lack of stereospecificity of the HSA-warfarin interaction. The conformation of the warfarin binding pocket is significantly altered upon binding of fatty acids, and this can explain the observed enhancement of warfarin binding to HSA at low levels of fatty acid. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Analbuminemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103600 103600]], Dysalbuminemic hyperthyroxinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103600 103600]], Dysalbuminemic hyperzincemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103600 103600]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Curry, S.]] | [[Category: Curry, S.]] | ||
[[Category: Petitpas, I.]] | [[Category: Petitpas, I.]] | ||
| - | [[Category: MYR]] | ||
| - | [[Category: WRS]] | ||
[[Category: anti-coagulant]] | [[Category: anti-coagulant]] | ||
[[Category: drug binding]] | [[Category: drug binding]] | ||
[[Category: serum protein]] | [[Category: serum protein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:00:58 2008'' |
Revision as of 18:01, 30 March 2008
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| , resolution 2.50Å | |||||||
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| Sites: | |||||||
| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID AND THE S-(-) ENANTIOMER OF WARFARIN
Overview
Human serum albumin (HSA) is an abundant transport protein found in plasma that binds a wide variety of drugs in two primary binding sites (I and II) and can have a significant impact on their pharmacokinetics. We have determined the crystal structures at 2.5 A-resolution of HSA-myristate complexed with the R-(+) and S-(-) enantiomers of warfarin, a widely used anticoagulant that binds to the protein with high affinity. The structures confirm that warfarin binds to drug site I (in subdomain IIA) in the presence of fatty acids and reveal the molecular details of the protein-drug interaction. The two enantiomers of warfarin adopt very similar conformations when bound to the protein and make many of the same specific contacts with amino acid side chains at the binding site, thus accounting for the relative lack of stereospecificity of the HSA-warfarin interaction. The conformation of the warfarin binding pocket is significantly altered upon binding of fatty acids, and this can explain the observed enhancement of warfarin binding to HSA at low levels of fatty acid.
About this Structure
1HA2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I., Petitpas I, Bhattacharya AA, Twine S, East M, Curry S, J Biol Chem. 2001 Jun 22;276(25):22804-9. Epub 2001 Apr 2. PMID:11285262
Page seeded by OCA on Sun Mar 30 21:00:58 2008
