Our research is focused on revealing the transport mechanism of membrane
proteins through determination of their structure by nuclear magnetic
resonance (NMR) spectroscopy. Membrane transport proteins regulate cellular
events by acting as gatekeepers of ions, drugs and other essential molecules. Since about half of the drugs on the market target membrane
embedded proteins, knowledge of how and why these molecules bind and
cause biological activation (or inactivation) is of paramount importance.
NMR is particularly well-suited to reveal both the structure and dynamics of these challenging proteins under native membrane
conditions without the need for crystallization.
Multidrug resistance is a serious problem in the treatment of infectious diseases. The Institute of Allergy and Infectious Diseases indicates that many diseases are now becoming difficult to treat due to antimicrobial-resistant organisms. Some of these infectious diseases include HIV, tuberculosis, meningitis, staphylococcal infection, influenza, gonorrhea, Candida, and malaria (http://www.cdc.gov/drugresistance/about.html).
Bacteria gain resistance to drugs by
a number of mechanisms including: efflux of antibiotics, mutation, permeability
of the cell wall, alterations to the antibiotic, changes to the binding
sites of antibiotics, or deactivation of the drug molecules. One of the broadest defense mechanisms is through a rather simple mechanism: sending the drug out of the
cell. This is the mode of function for the small multidrug resistance (SMR) family of ion-transporter proteins consist of four
transmembrane domains and ~110 residues. SMR proteins confer
resistance to several quaternary ammonium compounds and other lipophilic
cations that are commonly used in spray-fogging procedures for hospital
rooms to reduce the number of airborne and surface bacteria. Our NMR experiments are aimed at understanding the mechanism of substrate specificity and the ion-coupled transport mechanism
An Agilent DD2 NMR Spectrometer (600 MHz) is used solely by the Traaseth lab for solid-state NMR experiments.