The crystal structure of an odorant binding protein from Anopheles gambiae: evidence for a common ligand release mechanism.
The Anopheles gambiae mosquito is the main vector of malaria transmission in sub-Saharan Africa. We present here a 1.5A 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.
Wogulis
Mark
M
Section of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
Morgan
Tania
T
Ishida
Yuko
Y
Leal
Walter S
WS
Wilson
David K
DK
D000818:Animals; D000852:Anopheles / Q000737:chemistry*; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D018035:Receptors, Odorant / Q000737:chemistry*
D008024:Ligands; D018035:Receptors, Odorant