1e7c: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
Human serum albumin (HSA) is one of the most abundant proteins in the | 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== | ==Disease== | ||
| Line 16: | Line 16: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bhattacharya, A | [[Category: Bhattacharya, A A.]] | ||
[[Category: Curry, S.]] | [[Category: Curry, S.]] | ||
[[Category: Franks, N | [[Category: Franks, N P.]] | ||
[[Category: HLT]] | [[Category: HLT]] | ||
[[Category: MYR]] | [[Category: MYR]] | ||
| Line 27: | Line 27: | ||
[[Category: plasma protein]] | [[Category: plasma protein]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:24:39 2008'' | ||
Revision as of 13:24, 21 February 2008
|
HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID AND 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
1E7C is a Single protein structure of sequence from Homo sapiens with and as ligands. 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
Page seeded by OCA on Thu Feb 21 12:24:39 2008