2WNJ: Crystal Structure Of Aplysia Achbp In Complex With Dmxba

Citation:
Abstract
The pentameric acetylcholine-binding protein (AChBP) is a soluble surrogate of the ligand binding domain of nicotinic acetylcholine receptors. Agonists bind within a nest of aromatic side chains contributed by loops C and F on opposing faces of each subunit interface. Crystal structures of Aplysia AChBP bound with the agonist anabaseine, two partial agonists selectively activating the alpha7 receptor, 3-(2,4-dimethoxybenzylidene)-anabaseine and its 4-hydroxy metabolite, and an indole-containing partial agonist, tropisetron, were solved at 2.7-1.75 A resolution. All structures identify the Trp 147 carbonyl oxygen as the hydrogen bond acceptor for the agonist-protonated nitrogen. In the partial agonist complexes, the benzylidene and indole substituent positions, dictated by tight interactions with loop F, preclude loop C from adopting the closed conformation seen for full agonists. Fluctuation in loop C position and duality in ligand binding orientations suggest molecular bases for partial agonism at full-length receptors. This study, while pointing to loop F as a major determinant of receptor subtype selectivity, also identifies a new template region for designing alpha7-selective partial agonists to treat cognitive deficits in mental and neurodegenerative disorders.
PDB ID: 2WNJDownload
MMDB ID: 76377
PDB Deposition Date: 2009/7/9
Updated in MMDB: 2009/11
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2WNJ: pentameric; determined by author and by software (PISA)
Molecular Components in 2WNJ
Label Count Molecule
Proteins (5 molecules)
5
Soluble Acetylcholine Receptor
Molecule annotation
Chemicals (10 molecules)
1
5
2
3
3
1
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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