Tan, Kelly R; Baur, Roland; Charon, Sébastien; Goeldner, Maurice; Sigel, Erwin (2009). Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors. Journal of neurochemistry, 111(5), pp. 1264-73. Oxford: Wiley-Blackwell 10.1111/j.1471-4159.2009.06419.x
Full text not available from this repository. (Request a copy)GABA(A) receptors are the major inhibitory neurotransmitter receptors in the brain. Some of them are targets of benzodiazepines that are widely used in clinical practice for their sedative/hypnotic, anxiolytic, muscle relaxant and anticonvulsant effects. In order to rationally separate these different drug actions, we need to understand the interaction of such compounds with the benzodiazepine-binding pocket. With this aim, we mutated residues located in the benzodiazepine-binding site individually to cysteine. These mutated receptors were combined with benzodiazepine site ligands carrying a cysteine reactive group in a defined position. Proximal apposition of reaction partners will lead to a covalent reaction. We describe here such proximity-accelerated chemical coupling reactions of alpha(1)S205C and alpha(1)T206C with a diazepam derivative modified at the C-3 position with a reactive isothiocyanate group (-NCS). We also provide new data that identify alpha(1)H101C and alpha(1)N102C as exclusive sites of the reaction of a diazepam derivative where the -Cl atom is replaced by a -NCS group. Based on these observations we propose a relative positioning of diazepam within the benzodiazepine-binding site of alpha(1)beta(2)gamma(2) receptors.
Item Type: |
Journal Article (Original Article) |
---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
UniBE Contributor: |
Baur, Roland, Sigel, Erwin |
ISSN: |
0022-3042 |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:12 |
Last Modified: |
05 Dec 2022 14:22 |
Publisher DOI: |
10.1111/j.1471-4159.2009.06419.x |
PubMed ID: |
19804380 |
Web of Science ID: |
000271496500017 |
URI: |
https://boris.unibe.ch/id/eprint/31632 (FactScience: 196263) |