Abstract
The Anopheles gambiae mosquito is the main vector of malaria transmission in sub-Saharan Africa. We present here a 1.5 Å crystal structure of AgamOBP1, an odorant binding protein (OBP) from the A. gambiae mosquito. The protein crystallized as a dimer with a unique binding pocket consisting of a continuous tunnel running through both subunits of the dimer and occupied by a PEG molecule. We demonstrate that AgamOBP1 undergoes a pH dependent conformational change that is associated with reduced ligand binding. A predominance of acid-labile hydrogen bonds involving the C-terminal loop suggests a mechanism in which a drop in pH causes C-terminal loop to open, leaving the binding tunnel solvent exposed, thereby lowering binding affinity for ligand. Because proteins from two distantly related insects also undergo a pH dependent conformational change involving the C-terminus that is associated with reduced ligand affinity, our results suggest a common mechanism for OBP activity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 157-164 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 339 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 6 2006 |
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Keywords
- Anopheles gambiae
- Crystal structure
- Ligand binding
- Malaria
- Olfaction
- pH dependent binding
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
The crystal structure of an odorant binding protein from Anopheles gambiae : Evidence for a common ligand release mechanism. / Wogulis, Mark; Morgan, Tania; Ishida, Yuko; Leal, Walter S.; Wilson, David K.
In: Biochemical and Biophysical Research Communications, Vol. 339, No. 1, 06.01.2006, p. 157-164.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The crystal structure of an odorant binding protein from Anopheles gambiae
T2 - Evidence for a common ligand release mechanism
AU - Wogulis, Mark
AU - Morgan, Tania
AU - Ishida, Yuko
AU - Leal, Walter S.
AU - Wilson, David K.
PY - 2006/1/6
Y1 - 2006/1/6
N2 - The Anopheles gambiae mosquito is the main vector of malaria transmission in sub-Saharan Africa. We present here a 1.5 Å crystal structure of AgamOBP1, an odorant binding protein (OBP) from the A. gambiae mosquito. The protein crystallized as a dimer with a unique binding pocket consisting of a continuous tunnel running through both subunits of the dimer and occupied by a PEG molecule. We demonstrate that AgamOBP1 undergoes a pH dependent conformational change that is associated with reduced ligand binding. A predominance of acid-labile hydrogen bonds involving the C-terminal loop suggests a mechanism in which a drop in pH causes C-terminal loop to open, leaving the binding tunnel solvent exposed, thereby lowering binding affinity for ligand. Because proteins from two distantly related insects also undergo a pH dependent conformational change involving the C-terminus that is associated with reduced ligand affinity, our results suggest a common mechanism for OBP activity.
AB - The Anopheles gambiae mosquito is the main vector of malaria transmission in sub-Saharan Africa. We present here a 1.5 Å crystal structure of AgamOBP1, an odorant binding protein (OBP) from the A. gambiae mosquito. The protein crystallized as a dimer with a unique binding pocket consisting of a continuous tunnel running through both subunits of the dimer and occupied by a PEG molecule. We demonstrate that AgamOBP1 undergoes a pH dependent conformational change that is associated with reduced ligand binding. A predominance of acid-labile hydrogen bonds involving the C-terminal loop suggests a mechanism in which a drop in pH causes C-terminal loop to open, leaving the binding tunnel solvent exposed, thereby lowering binding affinity for ligand. Because proteins from two distantly related insects also undergo a pH dependent conformational change involving the C-terminus that is associated with reduced ligand affinity, our results suggest a common mechanism for OBP activity.
KW - Anopheles gambiae
KW - Crystal structure
KW - Ligand binding
KW - Malaria
KW - Olfaction
KW - pH dependent binding
UR - http://www.scopus.com/inward/record.url?scp=28144452847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28144452847&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.10.191
DO - 10.1016/j.bbrc.2005.10.191
M3 - Article
C2 - 16300742
AN - SCOPUS:28144452847
VL - 339
SP - 157
EP - 164
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -