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 |
Keywords
- Anopheles gambiae
- Crystal structure
- Ligand binding
- Malaria
- Olfaction
- pH dependent binding
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology