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PDBsum entry 1oof
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Transport protein
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PDB id
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1oof
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of a specific alcohol-Binding site defined by the odorant binding protein lush from drosophila melanogaster.
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Authors
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S.W.Kruse,
R.Zhao,
D.P.Smith,
D.N.Jones.
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Ref.
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Nat Struct Biol, 2003,
10,
694-700.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Figure 1. Ribbon diagrams of LUSH and PBP. (a) Diagram of
LUSH -butanol structure solved to 1.25-Å resolution. Individual
helices are labeled  1
- 6.
5'
is a stretch of 3[10]-helix. Butanol is represented as a
space-filling model at the center of the protein. Alkyl chain,
cyan; hydroxyl group, red. (b) Diagram of PBP -bombykol complex
from B. mori. Elements of secondary structure are colored as for
LUSH. Bombykol is shown in a ball-and-stick representation.
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Figure 2.
Figure 2. Structure of LUSH alcohol-binding pocket. (a) Key
residues in alcohol-binding pocket formed by helix 3 (gold),
helix 6 (blue) and the C-terminal strand. Network of hydrogen
bonds formed by Thr48, Ser52, Thr57 and ethanol, red dotted
lines. (b) Stereo view of electron density of residues in
binding pocket of LUSH -ethanol complex. (c) Same view of
alcohol-binding pocket in LUSH -butanol complex.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2003,
10,
694-700)
copyright 2003.
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