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Cryo-EM of human glucagon-like peptide 1 receptor glp-1R bound to tirzepatide

Analyse Cryo-EM of human glucagon-like peptide 1 receptor glp-1R bound to tirzepatide in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
7RGP
Type
protein
Length
1,383 residues
Chains
7
Method
electron microscopy
Collection
MolNFT v1 / PDB
Contract
0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner
0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule
Guanine nucleotide-binding protein G(I) subunit alpha-3, isoform gnas-2 of guanine…
UniProt
P08754, P63092, P62873, P59768, P43220
Pockets
20 · best druggability 0.81

Structure

electron microscopy · 7 distinct chains · 30% helix, 26% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
AGuanine nucleotide-binding protein G(I) subunit alpha-3, isoform gnas-2 of guanine nucleotide-binding protein G(S) subunit alpha isoforms shortprotein21644% helix, 16% strandP08754, P63092
BGuanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1protein3397% helix, 47% strandP62873
ESingle-chain variable fragment 16protein2323% helix, 46% strand—
GGuanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2protein5951% helix, 0% strandP59768
NNanobody 35protein1287% helix, 43% strand—
PTirzepatideprotein3187% helix, 0% strand—
RGlucagon-like peptide 1 receptorprotein37860% helix, 2% strandP43220

Pockets

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

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
16350.810.8653empty
28930.780.8188empty
310100.770.7963empty
41700.700.8927empty
54070.650.7952empty

Interfaces

9 interfaces between chains.

  • B–G · 2056 Ų buried · 14 hydrogen bonds · protein-protein
  • P–R · 1677 Ų buried · 18 hydrogen bonds · protein-protein
  • A–B · 1478 Ų buried · 17 hydrogen bonds · protein-protein
  • A–R · 1069 Ų buried · 14 hydrogen bonds · protein-protein
  • A–N · 905 Ų buried · 10 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 8 disulfide, 2 modified (disulfide, nonstandard).

Compared structures

  • 7RGP · cryo-EM of human Glucagon-like peptide 1 receptor GLP-1R bound to tirzepatide · the same entry in another collection · chain R against R, TM-score 1.00
  • P62873 · 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
  • P59768 · 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 0.91
  • 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 0.83
  • P08754 · AlphaFold monomer V2.0 prediction for guanine nucleotide-binding protein G(I) subunit… · a predicted model of the same protein · chain A against A, TM-score 0.74

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