3b88 | pdb_00003b88

Complex of T57A Substituted Drosophila LUSH Protein with Ethanol

spinqualitylabelsall models 3b88, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3b88 is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, ETE Related: 1ooh, 1oof, 1oog, 1ooi, 1t14, 3b6x, 3b7a, 3b67, 3b86 Gene: lush, Obp76a, Obp76c (Drosophila melanogaster) Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Odorant binding protein

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