'''Crystal structure of LUSH from Drosophila melanogaster: apo protein'''
===Crystal structure of LUSH from Drosophila melanogaster: apo protein===
==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Odorant binding]]
[[Category: Odorant binding]]
[[Category: Transport protein]]
[[Category: Transport protein]]
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Revision as of 12:41, 29 July 2008
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The role of multiple hydrogen-bonding groups in specific alcohol binding sites in proteins: insights from structural studies of LUSH., Thode AB, Kruse SW, Nix JC, Jones DN, J Mol Biol. 2008 Mar 7;376(5):1360-76. Epub 2008 Jan 5. PMID:18234222
