An .alpha.-Bungarotoxin-Binding Sequence on the Torpedo Nicotinic Acetylcholine Receptor .alpha.-Subunit: Conservative Amino Acid Substitutions Reveal Side-Chain Specific Interactions

Biochemistry ◽  
1994 ◽  
Vol 33 (9) ◽  
pp. 2576-2585 ◽  
Author(s):  
Kathryn E. McLane ◽  
Xiadong Wu ◽  
Bianca M. Conti-Tronconi
Keyword(s):  
Amino Acid ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Alpha Subunit ◽  
Side Chain ◽  
Amino Acid Substitutions ◽  
Specific Interactions ◽  
Nicotinic Acetylcholine ◽  
Alpha Bungarotoxin ◽  
Binding Sequence

scholarly journals Sequence and functional expression of a single alpha subunit of an insect nicotinic acetylcholine receptor.

1990 ◽  
Vol 9 (13) ◽  
pp. 4391-4398 ◽  
Author(s):  
J. Marshall ◽  
S. D. Buckingham ◽  
R. Shingai ◽  
G. G. Lunt ◽  
M. W. Goosey ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Functional Expression ◽  
Alpha Subunit ◽  
Nicotinic Acetylcholine

scholarly journals In Silico Finding of Key Interaction Mediated α3β4 and α7 Nicotinic Acetylcholine Receptor Ligand Selectivity of Quinuclidine-Triazole Chemotype

2020 ◽  
Vol 21 (17) ◽  
pp. 6189
Author(s):  
Kuntarat Arunrungvichian ◽  
Sumet Chongruchiroj ◽  
Jiradanai Sarasamkan ◽  
Gerrit Schüürmann ◽  
Peter Brust ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
In Silico ◽  
Amino Acid Residues ◽  
Nicotinic Acetylcholine ◽  
Selective Binding ◽  
Ligand Selectivity ◽  
Α7 Nachr ◽  
Nachr Subtype

The selective binding of six (S)-quinuclidine-triazoles and their (R)-enantiomers to nicotinic acetylcholine receptor (nAChR) subtypes α3β4 and α7, respectively, were analyzed by in silico docking to provide the insight into the molecular basis for the observed stereospecific subtype discrimination. Homology modeling followed by molecular docking and molecular dynamics (MD) simulations revealed that unique amino acid residues in the complementary subunits of the nAChR subtypes are involved in subtype-specific selectivity profiles. In the complementary β4-subunit of the α3β4 nAChR binding pocket, non-conserved AspB173 through a salt bridge was found to be the key determinant for the α3β4 selectivity of the quinuclidine-triazole chemotype, explaining the 47–327-fold affinity of the (S)-enantiomers as compared to their (R)-enantiomer counterparts. Regarding the α7 nAChR subtype, the amino acids promoting a however significantly lower preference for the (R)-enantiomers were the conserved TyrA93, TrpA149 and TrpB55 residues. The non-conserved amino acid residue in the complementary subunit of nAChR subtypes appeared to play a significant role for the nAChR subtype-selective binding, particularly at the heteropentameric subtype, whereas the conserved amino acid residues in both principal and complementary subunits are essential for ligand potency and efficacy.

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