Specially Appointed Assis. Prof.
Content of research
Xenobiotic extruding pumps are recently known to be widely distributed in living organisms from mammalian to bacteria as a host-defense mechanism in cellular level. These pumps not only confer multidrug resistance of cancer cells and pathogenic bacteria but also cause hereditary diseases through the mutation. The purposes of our laboratory are to elucidate the molecular structures and the molecular mechanisms of these xenobiotic exporters and the roles of these exporters in cell functions.
We determined the crystal structure of bacterial major xenobiotic exporter AcrB and elucidated the molecular mechanism of xenobiotic export and the structural basis of multidrug recognition by determining the crystal structure of the drug-binding form of AcrB.
Current Research Programs
- 1. Investigation into the structural basis of multidrug recognition by exporters
- 2. Elucidation of the structure and mechanism of multidrug efflux complex
- 3. Physiological role of xenobiotic exporters
- 4. Development of universal inhibiter based on the crystal structures
- 5. Crystallographic analysis of various xenobiotic exporters
Figure / Graph
Schematic illustration of functional rotation model and remote conformational coupling for multi-drug efflux.
A torsion movement of transmembrane helix occurring with formation/dissociation of the Asp-Lys ion pair in the transmembrane domain causes the conformational change of the series of Access -> Binding -> Extrusion.