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Structure of the pentameric ligand-gated ion channel GLIC bound with anesthetic ketamine.
- Source :
-
Structure (London, England : 1993) [Structure] 2012 Sep 05; Vol. 20 (9), pp. 1463-9. - Publication Year :
- 2012
-
Abstract
- Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but a structural understanding of anesthetic action on pLGICs remains elusive. GLIC, a prokaryotic pLGIC, can be inhibited by anesthetics, including ketamine. The ketamine concentration leading to half-maximal inhibition of GLIC (58 μM) is comparable to that on neuronal nicotinic acetylcholine receptors. A 2.99 Å resolution X-ray structure of GLIC bound with ketamine revealed ketamine binding to an intersubunit cavity that partially overlaps with the homologous antagonist-binding site in pLGICs. The functional relevance of the identified ketamine site was highlighted by profound changes in GLIC activation upon cysteine substitution of the cavity-lining residue N152. The relevance is also evidenced by changes in ketamine inhibition upon the subsequent chemical labeling of N152C. The results provide structural insight into the molecular recognition of ketamine and are valuable for understanding the actions of anesthetics and other allosteric modulators on pLGICs.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Anesthetics, Dissociative pharmacology
Animals
Bacterial Proteins antagonists & inhibitors
Bacterial Proteins biosynthesis
Binding Sites
Cells, Cultured
Crystallography, X-Ray
Cyanobacteria
Hydrogen-Ion Concentration
Ketamine pharmacology
Ligand-Gated Ion Channels antagonists & inhibitors
Ligand-Gated Ion Channels biosynthesis
Models, Molecular
Oocytes drug effects
Oocytes metabolism
Protein Binding
Protein Structure, Quaternary
Protein Structure, Secondary
Xenopus
Anesthetics, Dissociative chemistry
Bacterial Proteins chemistry
Ketamine chemistry
Ligand-Gated Ion Channels chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1878-4186
- Volume :
- 20
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Structure (London, England : 1993)
- Publication Type :
- Academic Journal
- Accession number :
- 22958642
- Full Text :
- https://doi.org/10.1016/j.str.2012.08.009