Structure of a specific alcohol-binding site defined by the odorant binding protein LUSH from Drosophila melanogaster

• Published in: Nature structural & molecular biology Vol. 10; no. 9; pp. 694 - 700
• Main Authors: Jones, David N M, Kruse, Schoen W, Zhao, Rui, Smith, Dean P
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.09.2003
• Subjects: Alcohols - chemistry; Amino Acid Motifs; Amino Acid Sequence; Animals; Binding Sites; Butanols - chemistry; Crystallography, X-Ray; Drosophila melanogaster; Drosophila melanogaster - metabolism; Hydrogen Bonding; Ions; Ligands; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Conformation; Receptors, Odorant - chemistry; Serine - chemistry; Threonine - chemistry
• ISSN: 1072-8368; 1545-9993; 2331-365X; 1545-9985
• DOI: 10.1038/nsb960

We have solved the high-resolution crystal structures of the Drosophila melanogaster alcohol-binding protein LUSH in complex with a series of short-chain n-alcohols. LUSH is the first known nonenzyme protein with a defined in vivo alcohol-binding function. The structure of LUSH reveals a set of molecular interactions that define a specific alcohol-binding site. A group of amino acids, Thr57, Ser52 and Thr48, form a network of concerted hydrogen bonds between the protein and the alcohol that provides a structural motif to increase alcohol-binding affinity at this site. This motif seems to be conserved in a number of mammalian ligand-gated ion channels that are directly implicated in the pharmacological effects of alcohol. Further, these sequences are found in regions of ion channels that are known to confer alcohol sensitivity. We suggest that the alcohol-binding site in LUSH represents a general model for alcohol-binding sites in proteins.