Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP

FEBS Lett. 2007 Mar 6;581(5):935-8. doi: 10.1016/j.febslet.2007.01.073. Epub 2007 Feb 7.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry*
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Adenylyl Imidodiphosphate / chemistry*
  • Adenylyl Imidodiphosphate / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • Drug Stability
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Recombinant Proteins
  • Adenylyl Imidodiphosphate
  • Adenosine Triphosphatases