Dresden 2009 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 17: Poster II
BP 17.23: Poster
Mittwoch, 25. März 2009, 17:15–19:45, P3
Simulating E.coli’s Major Efflux Pump: The Extrusion Mechanism for Substrates — •R. Schulz1, A. Vargiu2, P. Ruggerone2, M. Schreiber3, and U. Kleinekathöfer1 — 1Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany — 2University of Cagliari, 09042 Monserrato (CA), Italy — 3Technische Universität Chemnitz, 09107 Chemnitz, Germany
Bacteria, such as E. coli, use multidrug efflux pumps to export toxic substrates through their cell membranes. The RND transporter of the AcrAB-TolC efflux pump is able to export structurally and chemically different substrates. This is one reason of the increasing antibiotic resistance of bacteria. The energy is converted in the transmembrane domain and transduced towards the periplasmic part and used there to initiate a three-cyclic peristaltic pumping [1]. The effects of conformational changes on the extrusion of drugs, which have been located into one of the proposed binding pockets, are assessed using different computational methods like targeted molecular dynamics (TMD). The mechanism of pumping is investigated in greater detail than ever before [2]. Within TMD, a linear transition between two conformations is described. To investigate the effect of the conformational changes a feasible substrate, doxorubicin, has been placed into one of the binding pockets. Previously, the conformational changes of TolC which lead to an opening of the aperture have been investigated [3].
[1] M. Seeger et al., Current Drug Targets 9, 729 (2008)
[2] G. Sennhauser et al., PLoS Biology 5, 106 (2007)
[3] R. Schulz et al., Biophysical Journal (accepted)