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Cryo-EM structure of the compound 2-bound human glp-1 receptor-gs complex

Analyse Cryo-EM structure of the compound 2-bound human glp-1 receptor-gs complex in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
7EVM
Type
protein
Length
1,037 residues
Chains
5
Method
electron microscopy
Collection
MolNFT v1 / PDB
Contract
0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner
0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule
Guanine nucleotide-binding protein G(S) subunit alpha isoforms short; Guanine…
UniProt
P63092, P54311, P63212, P43220
Ligands
CLR, HNO
Pockets
12 · best druggability 0.82

Structure

electron microscopy · 5 distinct chains · 38% helix, 25% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
AGuanine nucleotide-binding protein G(S) subunit alpha isoforms shortprotein23543% helix, 17% strandP63092
BGuanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1protein3389% helix, 48% strandP54311
GGuanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2protein5659% helix, 0% strandP63212
NNanobody-35protein1267% helix, 45% strand—
RGlucagon-like peptide 1 receptorprotein28280% helix, 0% strandP43220

Ligands and binding sites

  • CLR · Cholesterol · ligand · 6 copies · chains R
  • HNO · N-tert-butyl-6,7-bis(chloranyl)quinoxalin-2-amine · ligand · chains R

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

Pockets

12 pockets found on a 1 Å grid, 8 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
16250.820.8756empty
211360.760.7976empty
38430.740.7865empty
45310.670.7745empty
51450.580.8329empty

Interfaces

6 interfaces between chains.

  • B–G · 2172 Ų buried · 17 hydrogen bonds · protein-protein
  • A–B · 1474 Ų buried · 22 hydrogen bonds · protein-protein
  • A–R · 1140 Ų buried · 18 hydrogen bonds · protein-protein
  • A–N · 1024 Ų buried · 16 hydrogen bonds · protein-protein
  • B–N · 599 Ų buried · 9 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 3 disulfide, 1 covalent (disulfide, covalent ligand).

Compared structures

  • 7EVM · Cryo-EM structure of the compound 2-bound human GLP-1 receptor-Gs complex · the same entry in another collection · chain R against R, TM-score 1.00
  • P54311 · AlphaFold monomer V2.0 prediction for guanine nucleotide-binding protein G(I)/G(S)/G(T)… · a predicted model of the same protein · chain B against A, TM-score 0.99
  • P43220 · AlphaFold monomer V2.0 prediction for glucagon-like peptide 1 receptor (P43220) · a predicted model of the same protein · chain R against A, TM-score 0.97
  • P63212 · AlphaFold monomer V2.0 prediction for guanine nucleotide-binding protein G(I)/G(S)/G(O)… · a predicted model of the same protein · chain G against A, TM-score 0.74

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