Principal Investigator
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P6 Clemens Glaubitz
Professor
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Institute of Biophysical Chemistry,
Center for Biomolecular
Magnetic Resonance
Goethe-University Frankfurt a.M.
Max-von-Laue-Str. 9
60438 Frankfurt am Main, Germany
Phone +49 (0)69 79 82 99 27
Fax +49 (0)69 79 82 99 29
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P6 Structure and function of bacterial multidrug efflux pumps
Multidrug resistance is an important problem in cancer chemotherapy and in the treatment of infectious diseases. The most distinct mechanism for multidrug resistance is based on secondary and primary active transport proteins which extrude a wide range of antibiotics out of the cell.
The mechanism by which they recognize and transport drugs remains to be resolved. We use solid-state NMR in combination with other spectroscopic and biochemical methods to resolve the structure-function relationship of these proteins directly within the lipid bilayer. We study both ABC transporters (LmrA) and secondary drug-proton antiporters (EmrE, TBsmr, Hsmr). We are interested in key events and structural changes during the transport cycle, in characterising the properties of the drug binding pockets, and investigating the role of lipids and oligomerisation for protein activity.
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Publications
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Lopez, J.J., Kaiser, C., Asami, S. and Glaubitz, C. (2009) Higher sensitivity through selective 13C excitation in solid-state NMR spectroscopy. J Am Chem Soc 131, 15970-15971.
Hellmich, U.A. and Glaubitz, C. (2009) NMR and EPR Studies of Membrane Transporters. Biol Chem 390, 815-834.
Hellmich, U.A., Pfleger, N. and Glaubitz, C. (2009) 19F-MAS NMR on Proteorhodopsin: Enhanced protocol for site-specific labeling for general application to membrane proteins. Photochem Photobiol 85, 535-539.
Lehner, I., Basting, D., Meyer, B., Haase, W., Manolikas, T., Kaiser, C., Karas, M. and Glaubitz, C. (2008) The key residue for substrate transport in the EmrE dimer is asymmetric. J Biol Chem 283, 3281-3288.
Lopez, J.J., Shukla, A.K., Reinhart, C., Schwalbe, H., Michel, H. and Glaubitz, C. (2008) The structure of bradykinin bound to the human GPCR bradykinin-2 as determined by solid-state NMR. Angew Chem Int Ed 47, 1668-1671.
Basting*, D., Lorch*, M., Lehner, I. and Glaubitz, C. (2008) Transport cycle intermediate in small multidrug resistance protein is revealed by substrate fluorescence. FASEB J 22, 365-373.
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Collaborations
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Prisner (P7), Wachtveitl (P12), Mäntele (P5), Fendler/Bamberg (P10), Ziegler (P4), Schwalbe (P13), Wachtveitl (P12), Fendler/Bamberg (P10), Dötsch/Bernhard (P2), Kühlbrandt (P1), Gottschalk (P11), Abele (P9)