4Z90

ELIC bound with the anesthetic isoflurane in the resting state


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.

Chen, Q.Kinde, M.N.Arjunan, P.Wells, M.M.Cohen, A.E.Xu, Y.Tang, P.

(2015) Sci Rep 5: 13833-13833

  • DOI: https://doi.org/10.1038/srep13833
  • Primary Citation of Related Structures:  
    4Z90, 4Z91

  • PubMed Abstract: 

    Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6') and A244(13'). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6' or 13' support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs.


  • Organizational Affiliation

    Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15260, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Gamma-aminobutyric-acid receptor subunit beta-1
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J
322Dickeya dadantii 3937Mutation(s): 0 
Gene Names: Dda3937_00520
Membrane Entity: Yes 
UniProt
Find proteins for E0SJQ4 (Dickeya dadantii (strain 3937))
Explore E0SJQ4 
Go to UniProtKB:  E0SJQ4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupE0SJQ4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MES
Query on MES

Download Ideal Coordinates CCD File 
L [auth A]
M [auth A]
N [auth B]
O [auth C]
P [auth D]
L [auth A],
M [auth A],
N [auth B],
O [auth C],
P [auth D],
T [auth F],
U [auth G],
V [auth H],
W [auth I],
X [auth J]
2-(N-MORPHOLINO)-ETHANESULFONIC ACID
C6 H13 N O4 S
SXGZJKUKBWWHRA-UHFFFAOYSA-N
4LE
Query on 4LE

Download Ideal Coordinates CCD File 
K [auth A],
Q [auth E],
R [auth F],
S [auth F]
(2R)-2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane
C3 H2 Cl F5 O
PIWKPBJCKXDKJR-SFOWXEAESA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 105.848α = 90
b = 267.079β = 106.94
c = 111.128γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
SCALAdata scaling
PHENIXrefinement
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM056257
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM066358
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR37GM049202
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesT32GM075770

Revision History  (Full details and data files)

  • Version 1.0: 2015-09-16
    Type: Initial release
  • Version 1.1: 2017-09-06
    Changes: Author supporting evidence, Derived calculations
  • Version 1.2: 2019-12-25
    Changes: Author supporting evidence
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Refinement description