Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / chemistry*
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Adenosine Triphosphatases / chemistry
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Adenylyl Imidodiphosphate / chemistry*
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Adenylyl Imidodiphosphate / metabolism
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Crystallography, X-Ray
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Drug Stability
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Models, Molecular
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Protein Binding
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Protein Conformation
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Staphylococcus aureus / genetics
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Staphylococcus aureus / metabolism*
Substances
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ATP-Binding Cassette Transporters
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Bacterial Proteins
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Recombinant Proteins
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Adenylyl Imidodiphosphate
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Adenosine Triphosphatases