3WTN

Crystal Structure of Lymnaea stagnalis Acetylcholine Binding Protein Complexed with Desnitro-imidacloprid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.09 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.213 

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Ligand Structure Quality Assessment 


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Literature

Studies on an acetylcholine binding protein identify a basic residue in loop G on the beta 1 strand as a new structural determinant of neonicotinoid actions

Ihara, M.Okajima, T.Yamashita, A.Oda, T.Asano, T.Matsui, M.Sattelle, D.B.Matsuda, K.

(2014) Mol Pharmacol 86: 736-746

  • DOI: https://doi.org/10.1124/mol.114.094698
  • Primary Citation of Related Structures:  
    3WTH, 3WTI, 3WTJ, 3WTK, 3WTL, 3WTM, 3WTN, 3WTO

  • PubMed Abstract: 

    Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs). Their widespread use and possible risks to pollinators make it extremely urgent to understand the mechanisms underlying their actions on insect nAChRs. We therefore elucidated X-ray crystal structures of the Lymnaea stagnalis acetylcholine binding protein (Ls-AChBP) and its Gln55Arg mutant, more closely resembling insect nAChRs, in complex with a nitromethylene imidacloprid analog (CH-IMI) and desnitro-imidacloprid metabolite (DN-IMI) as well as commercial neonicotinoids, imidacloprid, clothianidin, and thiacloprid. Unlike imidacloprid, clothianidin, and CH-IMI, thiacloprid did not stack with Tyr185 in the wild-type Ls-AChBP, but did in the Gln55Arg mutant, interacting electrostatically with Arg55. In contrast, DN-IMI lacking the NO2 group was directed away from Lys34 and Arg55 to form hydrogen bonds with Tyr89 in loop A and the main chain carbonyl of Trp143 in loop B. Unexpectedly, we found that several neonicotinoids interacted with Lys34 in loop G on the β1 strand in the crystal structure of the Gln55Arg mutant. Basic residues introduced into the α7 nAChR at positions equivalent to AChBP Lys34 and Arg55 enhanced agonist actions of neonicotinoids, while reducing the actions of acetylcholine, (-)-nicotine, and DN-IMI. Thus, not only the basic residues in loop D, but also those in loop G determine the actions of neonicotinoids. These novel findings provide new insights into the modes of action of neonicotinoids and emerging derivatives.


  • Organizational Affiliation

    Department of Applied Biological Chemistry, Faculty of Agriculture, Kinki University, Nara, Japan (M.I., Ta.O., T.A., M.M., K.M.); Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan (To.O.); Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan (A.Y.); and The Wolfson Institute for Biomedical Research, Department of Medicine, University College London, London, United Kingdom (D.B.S.) makoto_i@nara.kindai.ac.jp kmatsuda@nara.kindai.ac.jp.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acetylcholine-binding protein
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J
214Lymnaea stagnalisMutation(s): 0 
UniProt
Find proteins for P58154 (Lymnaea stagnalis)
Explore P58154 
Go to UniProtKB:  P58154
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP58154
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
N2Y
Query on N2Y

Download Ideal Coordinates CCD File 
AB [auth F]
CA [auth C]
FB [auth G]
K [auth A]
LA [auth D]
AB [auth F],
CA [auth C],
FB [auth G],
K [auth A],
LA [auth D],
LB [auth H],
OB [auth I],
T [auth B],
TA [auth E],
VB [auth J]
(2Z)-1-[(6-chloropyridin-3-yl)methyl]imidazolidin-2-imine
C9 H11 Cl N4
UEQZFAGVRGWPDK-UHFFFAOYSA-N
CD
Query on CD

Download Ideal Coordinates CCD File 
AA [auth B]
BB [auth F]
CB [auth F]
DA [auth C]
DB [auth F]
AA [auth B],
BB [auth F],
CB [auth F],
DA [auth C],
DB [auth F],
EA [auth C],
EB [auth F],
FA [auth C],
GA [auth C],
GB [auth G],
HA [auth C],
HB [auth G],
IA [auth C],
IB [auth G],
JA [auth C],
JB [auth G],
KB [auth G],
L [auth A],
M [auth A],
MA [auth D],
MB [auth H],
N [auth A],
NA [auth D],
NB [auth H],
O [auth A],
OA [auth D],
P [auth A],
PA [auth D],
PB [auth I],
Q [auth A],
QA [auth D],
QB [auth I],
R [auth A],
RA [auth D],
RB [auth I],
S [auth A],
SA [auth D],
SB [auth I],
TB [auth I],
U [auth B],
UA [auth E],
UB [auth I],
V [auth B],
VA [auth E],
W [auth B],
WA [auth E],
WB [auth J],
X [auth B],
XA [auth E],
XB [auth J],
Y [auth B],
YA [auth E],
Z [auth B],
ZA [auth E]
CADMIUM ION
Cd
WLZRMCYVCSSEQC-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
BA [auth B],
KA [auth C]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
N2Y Binding MOAD:  3WTN Kd: 91 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.09 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.213 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.006α = 90
b = 118.401β = 90
c = 243.591γ = 90
Software Package:
Software NamePurpose
BBSdata collection
PHASERphasing
CNSrefinement
HKL-2000data reduction
SCALEPACKdata 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: 2015-02-04
    Type: Initial release
  • Version 1.1: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description