2ie6
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Annexin V under 2.0 MPa pressure of xenon
OverviewOverview
In contrast with most inhalational anesthetics, the anesthetic gases xenon, (Xe) and nitrous oxide (N(2)O) act by blocking the N-methyl-d-aspartate, (NMDA) receptor. Using x-ray crystallography, we examined the binding, characteristics of these two gases on two soluble proteins as structural, models: urate oxidase, which is a prototype of a variety of intracellular, globular proteins, and annexin V, which has structural and functional, characteristics that allow it to be considered as a prototype for the NMDA, receptor. The structure of these proteins complexed with Xe and N(2)O were, determined. One N(2)O molecule or one Xe atom binds to the same main site, in both proteins. A second subsite is observed for N(2)O in each case. The, gas-binding sites are always hydrophobic flexible cavities buried within, the monomer. Comparison of the effects of Xe and N(2)O on urate oxidase, and annexin V reveals an interesting relationship with the in vivo, pharmacological effects of these gases, the ratio of the gas-binding, sites' volume expansion and the ratio of the narcotic potency being, similar. Given these data, we propose that alterations of cytosolic, globular protein functions by general anesthetics would be responsible for, the early stages of anesthesia such as amnesia and hypnosis and that, additional alterations of ion-channel membrane receptor functions are, required for deeper effects that progress to "surgical" anesthesia.
About this StructureAbout this Structure
2IE6 is a Single protein structure of sequence from Rattus norvegicus with CA, SO4 and XE as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Protein crystallography under xenon and nitrous oxide pressure: comparison with in vivo pharmacology studies and implications for the mechanism of inhaled anesthetic action., Colloc'h N, Sopkova-de Oliveira Santos J, Retailleau P, Vivares D, Bonnete F, Langlois d'Estainto B, Gallois B, Brisson A, Risso JJ, Lemaire M, Prange T, Abraini JH, Biophys J. 2007 Jan 1;92(1):217-24. Epub 2006 Oct 6. PMID:17028130
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