Download Unraveling the substrate specificity of a new ABC

Unraveling the substrate specificity of a new ABC-transporter SAV1866
A. Beck1, P. Aenismaa1, R. Dawson2, K. Locher2 and A. Seelig1
1
Biozentrum der Universität Basel (Basel, CH)
2
ETH Zurich (Zurich, CH)
ATP driven efflux transporters, such as P-glycoprotein (P-gp) are of great importance for
the protection of the organism against toxins and drugs. They also contribute to multidrug
resistance (MDR) in the case of drug therapy. Recently a bacterial homologue of P-gp,
SAV1866 from Staphylococcus aureus could be crystallized to high resolution [1]. The
physiological function of SAV1866 is unknown to date. Due to its similarity to P-gp it
was suggested to be involved in multidrug resistance of Staphylococcus aureus. Here we
provide quantitative evidence that SAV1866 is able to transport structurally very diverse
drugs and moreover that it is able to transport an endogenous lipid. The substrate
specificity is broad and their affinity from the membrane to the transporter seems to be
due to H-bond formation as shown previously for P-gp [2]
[1] Dawson, R.J.P. and Locher, K.P. Nature 443, 180-5 (2006)
[2] Gatlik-Landwojtowicz, E., Aanismaa, P., Seelig A. Biochemistry 45(9), 3020-32
(2006).