title: Structure of a specific alcohol-binding site defined by the odorant binding protein LUSH from Drosophila melanogaster.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, M/S C236, 4200 East Ninth Avenue, Denver, Colorado 80262, USA.
authors.forename: Schoen W
authors.initials: SW
authors.lastname: Kruse
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Dean P
authors.initials: DP
authors.lastname: Smith
authors.forename: David N M
authors.initials: DN
authors.lastname: Jones
mesh_terms: D000438:Alcohols / Q000737:chemistry; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D000440:Butanols / Q000737:chemistry; D018360:Crystallography, X-Ray; D004331:Drosophila melanogaster / Q000378:metabolism*; D006860:Hydrogen Bonding; D007477:Ions; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D018035:Receptors, Odorant / Q000737:chemistry*; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
chemical_list: D000438:Alcohols; D000440:Butanols; D007477:Ions; D008024:Ligands; D018035:Receptors, Odorant; C045648:odorant-binding protein; D013912:Threonine; D012694:Serine