4F8H

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.99 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structure of the Pentameric Ligand-Gated Ion Channel GLIC Bound with Anesthetic Ketamine.

Pan, J.Chen, Q.Willenbring, D.Mowrey, D.Kong, X.P.Cohen, A.Divito, C.B.Xu, Y.Tang, P.

(2012) Structure 20: 1463-1469

  • DOI: https://doi.org/10.1016/j.str.2012.08.009
  • Primary Citation of Related Structures:  
    4F8H

  • 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.


  • Organizational Affiliation

    Department of Anesthesiology, Biomedical Science Tower 3, 3501 Fifth Avenue, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proton-gated ion channel
A, B, C, D, E
317Gloeobacter violaceus PCC 7421Mutation(s): 0 
Gene Names: glvIglr4197
Membrane Entity: Yes 
UniProt
Find proteins for Q7NDN8 (Gloeobacter violaceus (strain ATCC 29082 / PCC 7421))
Explore Q7NDN8 
Go to UniProtKB:  Q7NDN8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ7NDN8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PC1
Query on PC1

Download Ideal Coordinates CCD File 
H [auth A]
I [auth A]
L [auth B]
M [auth B]
P [auth C]
H [auth A],
I [auth A],
L [auth B],
M [auth B],
P [auth C],
Q [auth C],
U [auth D],
V [auth D],
Y [auth E],
Z [auth E]
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
C44 H88 N O8 P
NRJAVPSFFCBXDT-HUESYALOSA-N
LMD
Query on LMD

Download Ideal Coordinates CCD File 
G [auth A]
K [auth B]
O [auth C]
R [auth C]
T [auth D]
G [auth A],
K [auth B],
O [auth C],
R [auth C],
T [auth D],
X [auth E]
tetradecyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside
C26 H50 O11
UKPROSIGWJBJGA-IWODYCRQSA-N
RKE
Query on RKE

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B],
N [auth C],
S [auth D],
W [auth E]
(R)-ketamine
C13 H16 Cl N O
YQEZLKZALYSWHR-CYBMUJFWSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
RKE PDBBind:  4F8H IC50: 5.80e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.99 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 184.069α = 90
b = 132.742β = 103.61
c = 162.077γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
SOLVEphasing
PHENIXrefinement
XDSdata reduction
XDSdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-08-29
    Type: Initial release
  • Version 1.1: 2012-09-26
    Changes: Database references
  • Version 1.2: 2018-06-13
    Changes: Data collection
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description