1E7C

HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID and the general anesthetic halothane

Summary for 1E7C

• Entry DOI: 10.2210/pdb1e7c/pdb
• Related: 1AO6 1BJ5 1BKE 1BM0 1E78 1E7A 1E7B 1E7E 1E7F 1E7G 1E7H 1E7I 1UOR
• Descriptor: SERUM ALBUMIN, MYRISTIC ACID, 2-BROMO-2-CHLORO-1,1,1-TRIFLUOROETHANE, ... (4 entities in total)
• Functional Keywords: plasma protein, metal-binding, lipid-binding, general anesthetic, halothane
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P02768
• Total number of polymer chains: 1
• Total formula weight: 69094.75

Authors

Bhattacharya, A.A.,Curry, S.,Franks, N.P. (deposition date: 2000-08-26, release date: 2001-01-17, Last modification date: 2024-10-23)

Primary citation

Bhattacharya, A.A.,Curry, S.,Franks, N.P.
Binding of the General Anesthetics Propofol and Halothane to Human Serum Albumin. High Resolution Crystal Structures
J.Biol.Chem., 275:38731-, 2000

PubMed Abstract: 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.

PubMed: 10940303
DOI: 10.1074/JBC.M005460200

Experimental method

X-RAY DIFFRACTION (2.4 Å)