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Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein

Analyse Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
6NBH
Type
protein
Length
1,159 residues
Chains
6
Method
electron microscopy
Collection
MolNFT v1 / PDB
Contract
0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner
0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule
Parathyroid HORMONE/PARATHYROID hormone-related peptide receptor; Long-acting parathyroid…
UniProt
Q03431, P54311, P63212
Ligands
CLR, PLM
Pockets
18 · best druggability 0.85

Structure

electron microscopy · 6 distinct chains · 37% helix, 23% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
RParathyroid HORMONE/PARATHYROID hormone-related peptide receptorprotein37964% helix, 5% strandQ03431
PLong-acting parathyroid hormone analogprotein3485% helix, 0% strand—
AGs protein alpha subunitprotein22545% helix, 17% strand—
BGuanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1protein3387% helix, 45% strandP54311
GGuanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2protein5754% helix, 0% strandP63212
NNanobody-35protein1262% helix, 44% strand—

Ligands and binding sites

  • CLR · Cholesterol · ligand · 7 copies · chains R
  • PLM · Palmitic acid · ligand · 3 copies · chains R

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

Pockets

18 pockets found on a 1 Å grid, 11 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
19070.850.8776empty
29440.750.7876empty
38790.740.7869empty
45260.710.8070empty
52460.680.8421empty

Interfaces

7 interfaces between chains.

  • R–P · 2318 Ų buried · 12 hydrogen bonds · protein-protein
  • B–G · 2155 Ų buried · 12 hydrogen bonds · protein-protein
  • A–B · 1569 Ų buried · 20 hydrogen bonds · protein-protein
  • R–A · 1190 Ų buried · 10 hydrogen bonds · protein-protein
  • A–N · 993 Ų buried · 6 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 6 disulfide (disulfide).

Compared structures

  • 6NBH · Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting… · the same entry in another collection · chain N against N, 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
  • Q03431 · AlphaFold monomer V2.0 prediction for parathyroid HORMONE/PARATHYROID hormone-related… · a predicted model of the same protein · chain R against A, TM-score 0.96
  • 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 0.62

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