1e7b: Difference between revisions
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==Overview== | ==Overview== | ||
Human serum albumin (HSA) is one of the most abundant proteins in the, circulatory system and plays a key role in the transport of fatty acids, metabolites, and drugs. For many drugs, binding to serum albumin is a, critical determinant of their distribution and pharmacokinetics; however, there have as yet been no high resolution crystal structures published of, drug-albumin complexes. Here we describe high resolution crystal, structures of HSA with two of the most widely used general anesthetics, propofol and halothane. In addition, we describe a crystal structure of, HSA complexed with both halothane and the fatty acid, myristate. We show, that the intravenous anesthetic propofol binds at two discrete sites on, HSA in preformed pockets that have been shown to accommodate fatty acids., Similarly we show that the inhalational agent halothane binds (at, concentrations in the pharmacologically relevant range) at three sites, that are also fatty acid binding loci. At much higher halothane, concentrations, we have identified additional sites that are occupied. All, of the higher affinity anesthetic binding sites are amphiphilic in nature, with both polar and apolar parts, and anesthetic binding causes only minor, changes in local structure. | Human serum albumin (HSA) is one of the most abundant proteins in the, circulatory system and plays a key role in the transport of fatty acids, metabolites, and drugs. For many drugs, binding to serum albumin is a, critical determinant of their distribution and pharmacokinetics; however, there have as yet been no high resolution crystal structures published of, drug-albumin complexes. Here we describe high resolution crystal, structures of HSA with two of the most widely used general anesthetics, propofol and halothane. In addition, we describe a crystal structure of, HSA complexed with both halothane and the fatty acid, myristate. We show, that the intravenous anesthetic propofol binds at two discrete sites on, HSA in preformed pockets that have been shown to accommodate fatty acids., Similarly we show that the inhalational agent halothane binds (at, concentrations in the pharmacologically relevant range) at three sites, that are also fatty acid binding loci. At much higher halothane, concentrations, we have identified additional sites that are occupied. All, of the higher affinity anesthetic binding sites are amphiphilic in nature, with both polar and apolar parts, and anesthetic binding causes only minor, changes in local structure. | ||
==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: halothane]] | [[Category: halothane]] | ||
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Revision as of 17:33, 12 November 2007
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CRYSTAL STRUCTURE OF HUMAN SERUM ALBUMIN COMPLEXED WITH THE GENERAL ANESTHETIC HALOTHANE
OverviewOverview
Human serum albumin (HSA) is one of the most abundant proteins in the, circulatory system and plays a key role in the transport of fatty acids, metabolites, and drugs. For many drugs, binding to serum albumin is a, critical determinant of their distribution and pharmacokinetics; however, there have as yet been no high resolution crystal structures published of, drug-albumin complexes. Here we describe high resolution crystal, structures of HSA with two of the most widely used general anesthetics, propofol and halothane. In addition, we describe a crystal structure of, HSA complexed with both halothane and the fatty acid, myristate. We show, that the intravenous anesthetic propofol binds at two discrete sites on, HSA in preformed pockets that have been shown to accommodate fatty acids., Similarly we show that the inhalational agent halothane binds (at, concentrations in the pharmacologically relevant range) at three sites, that are also fatty acid binding loci. At much higher halothane, concentrations, we have identified additional sites that are occupied. All, of the higher affinity anesthetic binding sites are amphiphilic in nature, with both polar and apolar parts, and anesthetic binding causes only minor, changes in local structure.
DiseaseDisease
Known diseases associated with this structure: Analbuminemia OMIM:[103600], Dysalbuminemic hyperthyroxinemia OMIM:[103600], Dysalbuminemic hyperzincemia OMIM:[103600]
About this StructureAbout this Structure
1E7B is a Single protein structure of sequence from Homo sapiens with HLT as ligand. Structure known Active Sites: 1, AC1, AC2, AC3, AC4 and AC6. Full crystallographic information is available from OCA.
ReferenceReference
Binding of the general anesthetics propofol and halothane to human serum albumin. High resolution crystal structures., Bhattacharya AA, Curry S, Franks NP, J Biol Chem. 2000 Dec 8;275(49):38731-8. PMID:10940303
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