43SN image
Deposition Date 2026-07-15
Release Date 2026-08-26
Last Version Date 2026-09-16
Entry Detail
PDB ID:
43SN
Title:
Alpha-7 nicotinic acetylcholine receptor bound to inhibitory bicyclic peptide KP1877 in a resting state
Biological Source:
Source Organism(s):
Expression System(s):
Method Details:
Experimental Method:
Resolution:
2.71 Å
Aggregation State:
PARTICLE
Reconstruction Method:
SINGLE PARTICLE
Macromolecular Entities
Polymer Type:polypeptide(L)
Molecule:Neuronal acetylcholine recept
Gene (Uniprot):CHRNA7
Chain IDs:A, C, E, G, I
Chain Length:502
Number of Molecules:5
Biological Source:Homo sapiens
Polymer Type:polypeptide(L)
Molecule:synthetic peptide KP1877
Chain IDs:B, D, F, H, J
Chain Length:17
Number of Molecules:5
Biological Source:synthetic construct
Ligand Molecules
Primary Citation
Screening, synthesis and structural characterization of a novel bicyclic peptide inhibiting alpha 7 nicotinic acetylcholine receptor.
Chem.Commun.(Camb.) 62 17041 17045 (2026)
PMID: 42574057 DOI: 10.1039/d6cc03853k

Abstact

Peptides targeting the alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) represent promising candidates for therapeutic and chemical probe development. Here, we identified a novel bicyclic peptide KP1877 via phage-displayed peptide library screening followed by chemical synthesis of active analogs. Structural characterization reveals KP1877 adopts a unique bicyclic conformation distinct from known natural alpha7-nAChR-targeting peptides, and exerts potent inhibitory effect by stabilizing the closed, non-conducting state of the receptor via orthosteric binding.

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Primary Citation of related structures
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