PDBsum entry 1my4

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protein ligands metals Protein-protein interface(s) links
Membrane protein PDB id
Protein chains
258 a.a. *
IWD ×3
_ZN ×5
Waters ×474
* Residue conservation analysis
PDB id:
Name: Membrane protein
Title: Crystal structure of glutamate receptor ligand-binding core with iodo-willardiine in the zn crystal form
Structure: Glutamate receptor 2. Chain: a, b, c. Fragment: ligand binding core (s1s2j). Synonym: glur-2, glur-b, glur-k2, glutamate receptor ionotr 2. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
1.90Å     R-factor:   0.213     R-free:   0.262
Authors: R.Jin,E.Gouaux
Key ref:
R.Jin and E.Gouaux (2003). Probing the function, conformational plasticity, and dimer-dimer contacts of the GluR2 ligand-binding core: studies of 5-substituted willardiines and GluR2 S1S2 in the crystal. Biochemistry, 42, 5201-5213. PubMed id: 12731861 DOI: 10.1021/bi020632t
03-Oct-02     Release date:   10-Jun-03    
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Protein chains
Pfam   ArchSchema ?
P19491  (GRIA2_RAT) -  Glutamate receptor 2
883 a.a.
258 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     transport   1 term 
  Biochemical function     transporter activity     3 terms  


DOI no: 10.1021/bi020632t Biochemistry 42:5201-5213 (2003)
PubMed id: 12731861  
Probing the function, conformational plasticity, and dimer-dimer contacts of the GluR2 ligand-binding core: studies of 5-substituted willardiines and GluR2 S1S2 in the crystal.
R.Jin, E.Gouaux.
Numerous naturally occurring and synthetic alpha-amino acids act as agonists on (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole) propionic acid (AMPA) receptors but nevertheless display significant differences in their functional properties and modes of interaction. The 5-substituted willardiines are a series of compounds that exhibit a range of affinities, act as partial agonists, and give rise to intermediate levels of activation and desensitization. However, the molecular basis for the activities of 5-substituted willardiines has not been conclusively elaborated at the level of atomic resolution. Here we provide insight into the molecular basis of the potency and efficacy elicited by the 5-substituted willardiines on the basis of cocrystal structures with the GluR2 ligand-binding core. We also show that the crystallized ligand-binding core has an affinity for agonists similar to the ligand-binding core in solution. Analysis of multiple crystal lattices suggests modes by which the ligand-binding core dimers interact in the tetrameric receptor. These studies further our understanding of how subtle differences in the structures of agonists are correlated to changes in the conformation of residues and water molecules in the immediate binding pocket and to the degree of domain closure.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20713069 J.Pøhlsgaard, K.Frydenvang, U.Madsen, and J.S.Kastrup (2011).
Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators.
  Neuropharmacology, 60, 135-150.  
20155979 A.F.Petrik, M.P.Strub, and J.C.Lee (2010).
Energy transfer ligands of the GluR2 ligand binding core.
  Biochemistry, 49, 2051-2057.  
20877838 R.Edwards, J.Madine, L.Fielding, and D.A.Middleton (2010).
Measurement of multiple torsional angles from one-dimensional solid-state NMR spectra: application to the conformational analysis of a ligand in its biological receptor site.
  Phys Chem Chem Phys, 12, 13999-14008.  
21080238 T.Nakagawa (2010).
The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors.
  Mol Neurobiol, 42, 161-184.  
19284741 A.H.Ahmed, M.D.Thompson, M.K.Fenwick, B.Romero, A.P.Loh, D.E.Jane, H.Sondermann, and R.E.Oswald (2009).
Mechanisms of antagonism of the GluR2 AMPA receptor: structure and dynamics of the complex of two willardiine antagonists with the glutamate binding domain.
  Biochemistry, 48, 3894-3903.
PDB codes: 3h03 3h06
19003990 A.H.Ahmed, Q.Wang, H.Sondermann, and R.E.Oswald (2009).
Structure of the S1S2 glutamate binding domain of GLuR3.
  Proteins, 75, 628-637.
PDB codes: 3dln 3dp4 3dp6
19102704 A.Gill, A.Birdsey-Benson, B.L.Jones, L.P.Henderson, and D.R.Madden (2008).
Correlating AMPA receptor activation and cleft closure across subunits: crystal structures of the GluR4 ligand-binding domain in complex with full and partial agonists.
  Biochemistry, 47, 13831-13841.
PDB codes: 3en3 3epe
18795801 A.S.Maltsev, A.H.Ahmed, M.K.Fenwick, D.E.Jane, and R.E.Oswald (2008).
Mechanism of partial agonism at the GluR2 AMPA receptor: Measurements of lobe orientation in solution.
  Biochemistry, 47, 10600-10610.  
18214958 E.J.Bjerrum, and P.C.Biggin (2008).
Rigid body essential X-ray crystallography: distinguishing the bend and twist of glutamate receptor ligand binding domains.
  Proteins, 72, 434-446.  
18081322 K.A.Mankiewicz, A.Rambhadran, L.Wathen, and V.Jayaraman (2008).
Chemical interplay in the mechanism of partial agonist activation in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
  Biochemistry, 47, 398-404.  
18754610 L.A.Cruz, E.Estébanez-Perpiñá, S.Pfaff, S.Borngraeber, N.Bao, J.Blethrow, R.J.Fletterick, and P.M.England (2008).
6-Azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX) forms an irreversible bond to the active site of the GluR2 AMPA receptor.
  J Med Chem, 51, 5856-5860.
PDB code: 3bki
18387631 M.K.Fenwick, and R.E.Oswald (2008).
NMR spectroscopy of the ligand-binding core of ionotropic glutamate receptor 2 bound to 5-substituted willardiine partial agonists.
  J Mol Biol, 378, 673-685.  
18823129 T.Mamonova, M.J.Yonkunas, and M.G.Kurnikova (2008).
Energetics of the cleft closing transition and the role of electrostatic interactions in conformational rearrangements of the glutamate receptor ligand binding domain.
  Biochemistry, 47, 11077-11085.  
17337449 A.H.Ahmed, A.P.Loh, D.E.Jane, and R.E.Oswald (2007).
Dynamics of the S1S2 glutamate binding domain of GluR2 measured using 19F NMR spectroscopy.
  J Biol Chem, 282, 12773-12784.  
17581823 H.Hald, P.Naur, D.S.Pickering, D.Sprogøe, U.Madsen, D.B.Timmermann, P.K.Ahring, T.Liljefors, A.Schousboe, J.Egebjerg, M.Gajhede, and J.S.Kastrup (2007).
Partial agonism and antagonism of the ionotropic glutamate receptor iGLuR5: structures of the ligand-binding core in complex with domoic acid and 2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid.
  J Biol Chem, 282, 25726-25736.
PDB codes: 1vso 2pbw
17934637 K.A.Mankiewicz, and V.Jayaraman (2007).
Glutamate receptors as seen by light: spectroscopic studies of structure-function relationships.
  Braz J Med Biol Res, 40, 1419-1427.  
17362499 S.Gonin, P.Arnoux, B.Pierru, J.Lavergne, B.Alonso, M.Sabaty, and D.Pignol (2007).
Crystal structures of an Extracytoplasmic Solute Receptor from a TRAP transporter in its open and closed forms reveal a helix-swapped dimer requiring a cation for alpha-keto acid binding.
  BMC Struct Biol, 7, 11.
PDB codes: 2hzk 2hzl
16731549 W.Zhang, A.Robert, S.B.Vogensen, and J.R.Howe (2006).
The relationship between agonist potency and AMPA receptor kinetics.
  Biophys J, 91, 1336-1346.  
15996549 A.Inanobe, H.Furukawa, and E.Gouaux (2005).
Mechanism of partial agonist action at the NR1 subunit of NMDA receptors.
  Neuron, 47, 71-84.
PDB codes: 1y1m 1y1z 1y20
15755731 D.R.Madden, N.Armstrong, D.Svergun, J.Pérez, and P.Vachette (2005).
Solution X-ray scattering evidence for agonist- and antagonist-induced modulation of cleft closure in a glutamate receptor ligand-binding domain.
  J Biol Chem, 280, 23637-23642.  
15677325 M.H.Nanao, T.Green, Y.Stern-Bach, S.F.Heinemann, and S.Choe (2005).
Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid.
  Proc Natl Acad Sci U S A, 102, 1708-1713.
PDB code: 1yae
16099829 M.M.Holm, M.L.Lunn, S.F.Traynelis, J.S.Kastrup, and J.Egebjerg (2005).
Structural determinants of agonist-specific kinetics at the ionotropic glutamate receptor 2.
  Proc Natl Acad Sci U S A, 102, 12053-12058.  
15224382 K.Strømgaard, and I.Mellor (2004).
AMPA receptor ligands: synthetic and pharmacological studies of polyamines and polyamine toxins.
  Med Res Rev, 24, 589-620.  
15229875 M.Kubo, and E.Ito (2004).
Structural dynamics of an ionotropic glutamate receptor.
  Proteins, 56, 411-419.  
14977400 M.L.Mayer, and N.Armstrong (2004).
Structure and function of glutamate receptor ion channels.
  Annu Rev Physiol, 66, 161-181.  
14766177 M.S.Horning, and M.L.Mayer (2004).
Regulation of AMPA receptor gating by ligand binding core dimers.
  Neuron, 41, 379-388.  
15107472 P.E.Chen, A.R.Johnston, M.H.Mok, R.Schoepfer, and D.J.Wyllie (2004).
Influence of a threonine residue in the S2 ligand binding domain in determining agonist potency and deactivation rate of recombinant NR1a/NR2D NMDA receptors.
  J Physiol, 558, 45-58.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.