Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP.
Staphylococcus aureus Sav1866 is a bacterial homolog of the human ABC transporter Mdr1 that causes multidrug resistance in cancer cells. We report the crystal structure of Sav1866 in complex with adenosine-5'-(beta,gamma-imido)triphosphate (AMP-PNP) at 3.4A resolution and compare it with the previously determined structure of Sav1866 with bound ADP. Besides differences in the ATP-binding sites, no significant conformational changes were observed. The results confirm that the ATP-bound state of multidrug ABC transporters is coupled to an outward-facing conformation of the transmembrane domains.
Dawson
Roger J P
RJ
Institute of Molecular Biology and Biophysics, ETH Zurich HPK D14.3, 8093 Zurich, Switzerland.
Locher
Kaspar P
KP
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004355:Drug Stability; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D000266:Adenylyl Imidodiphosphate; D000251:Adenosine Triphosphatases