Aligned structures of FQX and DNQX bound to the GluR2 ligand-binding core (S1S2J). (A) FQX (blue ribbon), DNQX (gray ribbon), and CNQX (not shown) produce the same degree of closure of the ligand-binding core. (B) Close-up view of the ligand-binding core showing the residues in close proximity to the ligands FQX and DNQX. Glutamate (E) 705 adopts a different conformation in the FQX structure (blue sticks) than the DNQX structure (gray sticks) and CNQX structure (not shown).

Photochemistry of ANQX^a
a Upon irradiation with UV light, ANQX (1) forms a highly reactive nitrene (2), which forms two products within the S1S2J binding pocket. The intramolecular reaction results in the formation of FQX (3). The intermolecular reaction results in the formation of a covalent bond with Glu705 in the ligand-binding core (4).

Structural formulas and orientation of the quinoxaline-2,3-diones discussed in the present study within the GluR2 ligand-binding core (S1S2J). (A) The competitive antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and [1,2,5]oxadiazolo[3,4-G]quinoxaline-6,7(5H,8H)-dione 1-oxide (FQX). (B) Close-up views of DNQX, CNQX and FQX bound to the S1S2J.

Photocross-linking of ANQX to the GluR2 ligand-binding core (S1S2J) analyzed using mass spectrometry. (A) ESI-o-TOF mass spectrum of the S1S2J (32218 Da) following irradiation (90 s) in the absence (blue trace) and presence (red trace) of ANQX (100 μM). Irradiation in the presence of ANQX produces a new major peak (32438 Da) that corresponds to the expected increase in mass (+220 Da) for the ANQX–protein adduct. (B) Mass spectra (MS/MS) of the peptide fragment spanning Glu705 following irradiation (90s) in presence (top panel) and absence (bottom panel) of ANQX. Irradiation in presence of ANQX produced a new peak (m/z 1602.72, E*, top panel), corresponding to the expected mass increase for the formation of an ANQX adduct, and the loss of unlabeled Glu705 (m/z 1399.68, E, bottom panel) peak.