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Active state of GLUA1/2 in complex with tarp gamma 8, L-glutamate and ctz

Analyse Active state of GLUA1/2 in complex with tarp gamma 8, L-glutamate and ctz in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
7QHB
Type
protein
Length
1,962 residues
Chains
6
Method
electron microscopy
Collection
MolNFT v1 / PDB
Contract
0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner
0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule
Isoform flip of glutamate receptor 1; Isoform flip of glutamate receptor 2…
UniProt
P19490, P19491, Q8VHW5
Ligands
PAM, GLU, CYZ, 79N
Pockets
20 · best druggability 0.77

Structure

electron microscopy · 3 distinct chains · 50% helix, 12% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
A, CIsoform flip of glutamate receptor 1protein39848% helix, 12% strandP19490
B, DIsoform flip of glutamate receptor 2protein39848% helix, 14% strandP19491
I, JVoltage-dependent calcium channel gamma-8 subunitprotein18561% helix, 8% strandQ8VHW5

Ligands and binding sites

  • PAM · Palmitoleic acid · ligand · 14 copies · chains A, B, I, C, D, J
  • GLU · Glutamic acid · ligand · 4 copies · chains A, B, C, D
  • CYZ · Cyclothiazide · ligand · 4 copies · chains A, B, C, D
  • 79N · (2S)-2,3-dihydroxypropyl (7Z)-hexadec-7-enoate · ligand · 4 copies · chains A, D, B, C
  • OLC · (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate · additive · 2 copies · chains A, B, C, D

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

20 pockets found on a 1 Å grid, 18 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
14780.770.8546empty
25050.760.8457CYZ
31980.750.9148empty
45090.750.8358CYZ
5550.710.9816GLU

Interfaces

8 interfaces between chains.

  • C–D · 2775 Ų buried · 17 hydrogen bonds · protein-protein
  • A–B · 2772 Ų buried · 17 hydrogen bonds · protein-protein
  • A–D · 1821 Ų buried · 5 hydrogen bonds · protein-protein
  • B–C · 1819 Ų buried · 5 hydrogen bonds · protein-protein
  • A–J · 753 Ų buried · 3 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 8 disulfide (disulfide).

Compared structures

  • 7QHB · Active state of GluA1/2 in complex with TARP gamma 8, L-glutamate and CTZ · the same entry in another collection · chain J against J, TM-score 1.00
  • Q8VHW5 · AlphaFold monomer V2.0 prediction for voltage-dependent calcium channel gamma-8 subunit… · a predicted model of the same protein · chain I against A, TM-score 0.94
  • P19491 · AlphaFold monomer V2.0 prediction for glutamate receptor 2 (P19491) · a predicted model of the same protein · chain B against A, TM-score 0.87
  • P19490 · AlphaFold monomer V2.0 prediction for glutamate receptor 1 (P19490) · a predicted model of the same protein · chain A against A, TM-score 0.68

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