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

Schoen W. Kruse, Rui Zhao, Dean P. Smith, David N M Jones

Research output: Contribution to journalArticle

167 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)694-700
Number of pages7
JournalNature Structural Biology
Volume10
Issue number9
DOIs
StatePublished - Sep 1 2003

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Drosophila melanogaster
Binding Sites
Alcohols
odorant-binding protein
Ligand-Gated Ion Channels
Proteins
Molecular interactions
Ion Channels
Hydrogen
Carrier Proteins
Hydrogen bonds
Crystal structure
Pharmacology
Amino Acids

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Structure of a specific alcohol-binding site defined by the odorant binding protein LUSH from Drosophila melanogaster. / Kruse, Schoen W.; Zhao, Rui; Smith, Dean P.; Jones, David N M.

In: Nature Structural Biology, Vol. 10, No. 9, 01.09.2003, p. 694-700.

Research output: Contribution to journalArticle

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