3RTF

Chlorowillardiine bound to the ligand binding domain of GluA2

PDB DOI: https://doi.org/10.2210/pdb3RTF/pdb

Classification: TRANSPORT PROTEIN
Organism(s): Rattus norvegicus
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2011-05-03 Released: 2011-05-18
Deposition Author(s): Ahmed, A.H., Oswald, R.E.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.70 Å
R-Value Free: 0.203
R-Value Work: 0.182
R-Value Observed: 0.182

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Mechanisms of Modal Activation of GluA3 Receptors.

Poon, K., Ahmed, A.H., Nowak, L.M., Oswald, R.E.

(2011) Mol Pharmacol 80: 49-59

PubMed: 21464198 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1124/mol.111.071688
Primary Citation of Related Structures:
3RT6, 3RT8, 3RTF, 3RTW

PubMed Abstract:
AMPA receptors are the major excitatory neurotransmitter receptors in the central nervous system and are involved in numerous neurological disorders. An agonist-binding site is present in each of four subunits that form a functional channel. Binding consists of three steps: docking of agonist to the bilobed ligand binding domain (LBD), closure of the LBD, and increased stability of the closed-lobe conformation through interlobe hydrogen bonding. We describe GluA3 single channel currents activated by nitrowillardiine (NO(2)W) and chlorowillardiine (ClW) in the presence of cyclothiazide, in conjunction with crystal structures of GluA2 and GluA3 LBDs bound to fluorowillardiine (FW), ClW, and NO(2)W. When bound to NO(2)W or ClW, the GluA3 channel opens to three conductance levels with comparable open probabilities and displays modal behavior similar to that obtained with glutamate and FW as agonists (Poon et al., 2010). At lower concentrations, ClW evoked an alternate kinetic behavior, consisting of high open probability in lower conductance states. The structure of ClW bound to GluA3 LBD exhibits a unique partially open hydrogen bonding structure that may be associated with these alternative kinetics. NO(2)W evoked longer open times than seen for other agonists in high and very high modes. The structure ofGluA2 LBD bound to NO(2)W exhibits fully closed lobes with additional interlobe interactions mediated by the nitro group. Beyond differences in efficacy between full and partial agonists, the complexities of the single channel behavior of AMPA receptors may also be associated with small interactions that modify the stability of various degrees of closure.

Organizational Affiliation

Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.

Macromolecule Content

Total Structure Weight: 87.53 kDa
Atom Count: 7,146
Modelled Residue Count: 774
Deposited Residue Count: 774
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Glutamate receptor 2	A [auth B], B [auth D], C [auth F]	258	Rattus norvegicus	Mutation(s): 0 Gene Names: GluA2, Glur2, Gria2
UniProt
Find proteins for P19491 (Rattus norvegicus) Explore P19491 Go to UniProtKB: P19491
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P19491
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
CWD Query on CWD Download Ideal Coordinates CCD File SDF format, chain J [auth F] SDF format, chain D [auth B] SDF format, chain G [auth D] MOL2 format, chain J [auth F] MOL2 format, chain D [auth B] MOL2 format, chain G [auth D]	D [auth B], G [auth D], J [auth F]	3-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-L-alanine C₇ H₈ Cl N₃ O₄ HEHLSRRDKJVHOM-BYPYZUCNSA-N		Interactions Focus chain D [auth B] Focus chain G [auth D] Focus chain J [auth F] Interactions & Density Focus chain D [auth B] Focus chain G [auth D] Focus chain J [auth F]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain E [auth B] SDF format, chain F [auth B] SDF format, chain H [auth D] SDF format, chain I [auth D] SDF format, chain K [auth F] MOL2 format, chain E [auth B] MOL2 format, chain F [auth B] MOL2 format, chain H [auth D] MOL2 format, chain I [auth D] MOL2 format, chain K [auth F]	E [auth B], F [auth B], H [auth D], I [auth D], K [auth F]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain E [auth B] Focus chain F [auth B] Focus chain H [auth D] Focus chain I [auth D] Focus chain K [auth F] Interactions & Density Focus chain E [auth B] Focus chain F [auth B] Focus chain H [auth D] Focus chain I [auth D] Focus chain K [auth F]

Binding Affinity Annotations
ID	Source	Binding Affinity
CWD	PDBBind: 3RTF	Ki: 45 (nM) from 1 assay(s)
	BindingDB: 3RTF	Ki: min: 37, max: 561 (nM) from 5 assay(s)
	BindingDB: 3RTF	EC50: 2110 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.70 Å
R-Value Free: 0.203
R-Value Work: 0.182
R-Value Observed: 0.182
Space Group: P 2 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 48.137	α = 90
b = 113.928	β = 90
c = 163.333	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data collection
PHENIX	model building
PHENIX	refinement
HKL-2000	data reduction
HKL-2000	data scaling
PHENIX	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2011-05-18

Deposition Author(s):

Ahmed, A.H.

Oswald, R.E.

Revision History (Full details and data files)

Version 1.0: 2011-05-18
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2017-07-26
Changes: Data collection, Source and taxonomy
Version 1.3: 2023-09-13
Changes: Data collection, Database references, Derived calculations, Refinement description