1h9z
From Proteopedia
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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: serum protein]] | [[Category: serum protein]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:14:35 2007'' |
Revision as of 15:08, 12 November 2007
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HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID AND THE R-(+) ENANTIOMER OF WARFARIN
Contents |
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.
Disease
Known diseases associated with this structure: Analbuminemia OMIM:[103600], Dysalbuminemic hyperthyroxinemia OMIM:[103600], Dysalbuminemic hyperzincemia OMIM:[103600]
About this Structure
1H9Z is a Single protein structure of sequence from Homo sapiens with MYR and WRR as ligands. Structure known Active Site: WRR. 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 Mon Nov 12 17:14:35 2007
