Which atom in acetylcholine acts as a hydrogen bond acceptor in muscarinic receptor binding?

Which atom in acetylcholine acts as a hydrogen bond acceptor in muscarinic receptor binding?

• A. Nitrogen of quaternary ammonium
• B. Ester oxygen
• C. Methyl carbon
• D. Hydrogen

Answer: (B)

Hydrogen bonding in receptor–ligand interactions comes from lone-pair bearing atoms on the ligand or receptor forming hydrogen bonds with donors or acceptors in the other partner. In acetylcholine, the quaternary ammonium nitrogen is positively charged and has no lone pairs, so it cannot serve as a hydrogen-bond acceptor; it mainly forms ionic interactions in the binding site. The ester portion of acetylcholine provides oxygen atoms with lone pairs that can accept hydrogen bonds from donor groups in the muscarinic receptor. The carbonyl oxygen is a particularly strong hydrogen-bond acceptor, and the adjacent alkoxy oxygen can also participate. Therefore, the ester oxygen acts as the hydrogen-bond acceptor in this binding context.

Hydrogen bonding in receptor–ligand interactions comes from lone-pair bearing atoms on the ligand or receptor forming hydrogen bonds with donors or acceptors in the other partner. In acetylcholine, the quaternary ammonium nitrogen is positively charged and has no lone pairs, so it cannot serve as a hydrogen-bond acceptor; it mainly forms ionic interactions in the binding site. The ester portion of acetylcholine provides oxygen atoms with lone pairs that can accept hydrogen bonds from donor groups in the muscarinic receptor. The carbonyl oxygen is a particularly strong hydrogen-bond acceptor, and the adjacent alkoxy oxygen can also participate. Therefore, the ester oxygen acts as the hydrogen-bond acceptor in this binding context.