The crystal structure of an odorant binding protein from Anopheles gambiae: evidence for a common ligand release mechanism |
| |
Authors: | Wogulis Mark Morgan Tania Ishida Yuko Leal Walter S Wilson David K |
| |
Affiliation: | Section of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA. |
| |
Abstract: | 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. |
| |
Keywords: | Anopheles gambiae Olfaction Crystal structure Ligand binding pH dependent binding Malaria |
本文献已被 ScienceDirect PubMed 等数据库收录! |