1UW6

X-ray structure of acetylcholine binding protein (AChBP) in complex with nicotine

1UW6 の概要

• エントリーDOI: 10.2210/pdb1uw6/pdb
• 関連するPDBエントリー: 1I9B 1UV6 1UX2
• 分子名称: ACETYLCHOLINE-BINDING PROTEIN, (S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE (3 entities in total)
• 機能のキーワード: pentamer, igg fold, acetylcholine, nicotine, glycoprotein
• 由来する生物種: LYMNAEA STAGNALIS (GREAT POND SNAIL)
• 細胞内の位置: Secreted: P58154
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 483757.68

構造登録者

Celie, P.H.N.,Van Rossum-fikkert, S.E.,Van Dijk, W.J.,Brejc, K.,Smit, A.B.,Sixma, T.K. (登録日: 2004-01-30, 公開日: 2004-03-25, 最終更新日: 2024-11-13)

主引用文献

Celie, P.H.N.,Van Rossum-Fikkert, S.E.,Van Dijk, W.J.,Brejc, K.,Smit, A.B.,Sixma, T.K.
Nicotine and Carbamylcholine Binding to Nicotinic Acetylcholine Receptors as Studied in Achbp Crystal Structures
Neuron, 41:907-, 2004

PubMed Abstract: Nicotinic acetylcholine receptors are prototypes for the pharmaceutically important family of pentameric ligand-gated ion channels. Here we present atomic resolution structures of nicotine and carbamylcholine binding to AChBP, a water-soluble homolog of the ligand binding domain of nicotinic receptors and their family members, GABAA, GABAC, 5HT3 serotonin, and glycine receptors. Ligand binding is driven by enthalpy and is accompanied by conformational changes in the ligand binding site. Residues in the binding site contract around the ligand, with the largest movement in the C loop. As expected, the binding is characterized by substantial aromatic and hydrophobic contributions, but additionally there are close contacts between protein oxygens and positively charged groups in the ligands. The higher affinity of nicotine is due to a main chain hydrogen bond with the B loop and a closer packing of the aromatic groups. These structures will be useful tools for the development of new drugs involving nicotinic acetylcholine receptor-associated diseases.

PubMed: 15046723
DOI: 10.1016/S0896-6273(04)00115-1

実験手法

X-RAY DIFFRACTION (2.2 Å)