1T14

Crystal structure of LUSH from Drosophila melanogaster: apo protein

1T14 の概要

• エントリーDOI: 10.2210/pdb1t14/pdb
• 関連するPDBエントリー: 1OOF 1OOG 1OOH 1OOI
• 分子名称: lush, ACETATE ION (3 entities in total)
• 機能のキーワード: lush, alcohol, odorant binding, transport protein
• 由来する生物種: Drosophila melanogaster (fruit fly)
• 細胞内の位置: Secreted: O02372
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28549.10

構造登録者

Kruse, S.W.,Jones, D.N.M. (登録日: 2004-04-15, 公開日: 2005-04-26, 最終更新日: 2024-10-30)

主引用文献

Thode, A.B.,Kruse, S.W.,Nix, J.C.,Jones, D.N.
The role of multiple hydrogen-bonding groups in specific alcohol binding sites in proteins: insights from structural studies of LUSH.
J.Mol.Biol., 376:1360-1376, 2008

PubMed Abstract: It is now generally accepted that many of the physiological effects of alcohol consumption are a direct result of binding to specific sites in neuronal proteins such as ion channels or other components of neuronal signaling cascades. Binding to these targets generally occurs in water-filled pockets and leads to alterations in protein structure and dynamics. However, the precise interactions required to confer alcohol sensitivity to a particular protein remain undefined. Using information from the previously solved crystal structures of the Drosophila melanogaster protein LUSH in complexes with short-chain alcohols, we have designed and tested the effects of specific amino acid substitutions on alcohol binding. The effects of these substitutions, specifically S52A, T57S, and T57A, were examined using a combination of molecular dynamics, X-ray crystallography, fluorescence spectroscopy, and thermal unfolding. These studies reveal that the binding of ethanol is highly sensitive to small changes in the composition of the alcohol binding site. We find that T57 is the most critical residue for binding alcohols; the T57A substitution completely abolishes binding, while the T57S substitution differentially affects ethanol binding compared to longer-chain alcohols. The additional requirement for a potential hydrogen-bond acceptor at position 52 suggests that both the presence of multiple hydrogen-bonding groups and the identity of the hydrogen-bonding residues are critical for defining an ethanol binding site. These results provide new insights into the detailed chemistry of alcohol's interactions with proteins.

PubMed: 18234222
DOI: 10.1016/j.jmb.2007.12.063

実験手法

X-RAY DIFFRACTION (1.86 Å)