4HFH

The GLIC pentameric Ligand-Gated Ion Channel (wild-type) complexed to bromoform


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel.

Sauguet, L.Howard, R.J.Malherbe, L.Lee, U.S.Corringer, P.J.Harris, R.A.Delarue, M.

(2013) Nat Commun 4: 1697-1697

  • DOI: https://doi.org/10.1038/ncomms2682
  • Primary Citation of Related Structures:  
    4HFB, 4HFC, 4HFD, 4HFE, 4HFH

  • PubMed Abstract: 

    Ethanol alters nerve signalling by interacting with proteins in the central nervous system, particularly pentameric ligand-gated ion channels. A recent series of mutagenesis experiments on Gloeobacter violaceus ligand-gated ion channel, a prokaryotic member of this family, identified a single-site variant that is potentiated by pharmacologically relevant concentrations of ethanol. Here we determine crystal structures of the ethanol-sensitized variant in the absence and presence of ethanol and related modulators, which bind in a transmembrane cavity between channel subunits and may stabilize the open form of the channel. Structural and mutagenesis studies defined overlapping mechanisms of potentiation by alcohols and anaesthetics via the inter-subunit cavity. Furthermore, homology modelling show this cavity to be conserved in human ethanol-sensitive glycine and GABA(A) receptors, and to involve residues previously shown to influence alcohol and anaesthetic action on these proteins. These results suggest a common structural basis for ethanol potentiation of an important class of targets for neurological actions of ethanol.


  • Organizational Affiliation

    Unité de Dynamique Structurale des Macromolécules, Institut Pasteur, F-75015 Paris, France.


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 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PLC
Query on PLC

Download Ideal Coordinates CCD File 
BB [auth E]
CB [auth E]
FA [auth C]
G [auth A]
GA [auth C]
BB [auth E],
CB [auth E],
FA [auth C],
G [auth A],
GA [auth C],
H [auth A],
QA [auth D],
RA [auth D],
U [auth B],
V [auth B]
DIUNDECYL PHOSPHATIDYL CHOLINE
C32 H65 N O8 P
IJFVSSZAOYLHEE-SSEXGKCCSA-O
LMT
Query on LMT

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BA [auth B]
IB [auth E]
MA [auth C]
P [auth A]
Q [auth A]
BA [auth B],
IB [auth E],
MA [auth C],
P [auth A],
Q [auth A],
XA [auth D]
DODECYL-BETA-D-MALTOSIDE
C24 H46 O11
NLEBIOOXCVAHBD-QKMCSOCLSA-N
MBR
Query on MBR

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CA [auth B]
DA [auth B]
JB [auth E]
KB [auth E]
NA [auth C]
CA [auth B],
DA [auth B],
JB [auth E],
KB [auth E],
NA [auth C],
OA [auth C],
R [auth A],
S [auth A],
YA [auth D],
ZA [auth D]
TRIBROMOMETHANE
C H Br3
DIKBFYAXUHHXCS-UHFFFAOYSA-N
ACT
Query on ACT

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AA [auth B]
AB [auth E]
EA [auth C]
F [auth A]
HB [auth E]
AA [auth B],
AB [auth E],
EA [auth C],
F [auth A],
HB [auth E],
LA [auth C],
O [auth A],
PA [auth D],
T [auth B],
WA [auth D]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
CL
Query on CL

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FB [auth E]
JA [auth C]
K [auth A]
L [auth A]
M [auth A]
FB [auth E],
JA [auth C],
K [auth A],
L [auth A],
M [auth A],
UA [auth D],
Y [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

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GB [auth E],
KA [auth C],
N [auth A],
VA [auth D],
Z [auth B]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
UNL
Query on UNL

Download Ideal Coordinates CCD File 
DB [auth E]
EB [auth E]
HA [auth C]
I [auth A]
IA [auth C]
DB [auth E],
EB [auth E],
HA [auth C],
I [auth A],
IA [auth C],
J [auth A],
SA [auth D],
TA [auth D],
W [auth B],
X [auth B]
Unknown ligand
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 181α = 90
b = 132.65β = 102.16
c = 159.27γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
SCALAdata 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: 2013-04-17
    Type: Initial release
  • Version 1.1: 2013-07-03
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations