2XNT: Acetylcholine Binding Protein (Achbp) As Template For Hierarchical In Silico Screening Procedures To Identify Structurally Novel Ligands For The Nicotinic Receptors

Hierarchical in silico screening protocols against the agonist bound acetylcholine binding protein (AChBP) crystal structure were efficient in identifying novel chemotypes for AChBP and the human alpha7 receptor. Two hit structures were cocrystallized with AChBP revealing intermolecular cation-pi interactions with loop C but lacking intermolecular hydrogen bonding. The compounds act as competitive alpha7 receptor antagonists and as non-competitive alpha4beta2 receptor inhibitors. These results underline the usability of AChBP in structure-based in silico screening strategies in finding novel scaffolds for the alpha7 receptor, but also illustrates some limitations of using AChBP as bait to find competitive alpha4beta2 receptor ligands and alpha7 receptor agonists.
PDB ID: 2XNTDownload
MMDB ID: 92829
PDB Deposition Date: 2010/8/6
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 3.21  Å
Source Organism:
Similar Structures:
Biological Unit for 2XNT: pentameric; determined by author and by software (PISA)
Molecular Components in 2XNT
Label Count Molecule
Proteins (5 molecules)
Soluble Acetylcholine Receptor
Molecule annotation
Chemicals (10 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB