4F8H

X-ray Structure of the Anesthetic Ketamine Bound to the GLIC Pentameric Ligand-gated Ion Channel

Summary for 4F8H

• Entry DOI: 10.2210/pdb4f8h/pdb
• Descriptor: Proton-gated ion channel, (R)-ketamine, tetradecyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, ... (5 entities in total)
• Functional Keywords: ketamine, pentameric ligand-gated ion channel, ion channel, anesthetics, transport protein
• Biological source: Gloeobacter violaceus
• Total number of polymer chains: 5
• Total formula weight: 193710.70

Authors

Pan, J.J.,Chen, Q.,Willenbring, D.,Kong, X.P.,Cohen, A.,Xu, Y.,Tang, P. (deposition date: 2012-05-17, release date: 2012-08-29, Last modification date: 2023-09-13)

Primary citation

Pan, J.,Chen, Q.,Willenbring, D.,Mowrey, D.,Kong, X.P.,Cohen, A.,Divito, C.B.,Xu, Y.,Tang, P.
Structure of the Pentameric Ligand-Gated Ion Channel GLIC Bound with Anesthetic Ketamine.
Structure, 20:1463-1469, 2012

PubMed 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.

PubMed: 22958642
DOI: 10.1016/j.str.2012.08.009

Experimental method

X-RAY DIFFRACTION (2.99 Å)