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)69 798-29927
Fax +49 (0)69 798-29929
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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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Hempelmann, F., Hölper, S., Verhoefen, M.K., Wörner, A., Köhler, T., Fiedler, S.A., Pfleger, N., Wachtveitl., S. and Glaubitz, C. (2011) The His75-Asp97 Cluster in Green Proteorhodopsin. J Am Chem Soc 133, 4645-4654.
Yang, J., Aslimovska, L. and Glaubitz, C. (2011) Molecular Dynamics of Green Proteo-rhodopsin in Lipid Bilayers by Solid-State NMR. J Am Chem Soc 133, 4874-4881.
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.
Hellmich, U.A., Haase, W., Velamakanni, S., van Veen, H. and Glaubitz, C. (2008) Caught in the Act: ATP hydrolysis of an ABC-Multidrug transporter followed by real-time Magic Angle Spinning NMR. Febs Letters 582, 3557-3562.
Lehner, I., Basting, D., Meyer, B., Haase, W., Manolikas, T., Kaiser, C., Karas, M. and Glaubitz C. (2008) The key residue for substrate transpor in the EmrE dimer is asymmetric. J Biol Chem 283, 3281-3288.
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), Dötsch/Bernhard (P2), Kühlbrandt (P1), Gottschalk (P11), Abele (P9)