pH-Dependent conformational states of AcrA protein: Implications for the assembly of AcrAB-TolC multidrug efflux pump

COMP 193

Jason Wallace, jason.wallace@ou.edu, Department of Chemistry and Biochemisty, The Univeristy of Oklahoma, 1510 E Lindsey Apt. F, Norman, OK 73071
In gram-negative bacteria much of the drug resistance is acquired by increased expression of multidrug efflux pumps. The most common multidrug efflux system is the resistance-nodulation cell division type such as the AcrAB-TolC system of Escherichia coli. AcrA has been shown experimentally to undergo a reversible pH induced conformational change that regulates the AcrA-TolC binding affinity. We have conducted constant pH molecular dynamics studies on AcrA and have identified residues that may be the source of the pH dependent behavior. These results support the suggestion that periplasmic pH may help regulate the assembly of the complex and possibly aid in substrate extrusion. Our hypothesis regarding the role of the specific residues in TolC binding is currently being tested by our collaborators. The identification of the origin of the pH dependent conformational states of AcrA may provide the ground work for the design of strategies to disable the efflux system.

 

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009