title: Structure of the ArsA ATPase: the catalytic subunit of a heavy metal resistance pump.
abstract: Active extrusion is a common mechanism underlying detoxification of heavy metals, drugs and antibiotics in bacteria, protozoa and mammals. In Escherichia coli, the ArsAB pump provides resistance to arsenite and antimonite. This pump consists of a soluble ATPase (ArsA) and a membrane channel (ArsB). ArsA contains two nucleotide-binding sites (NBSs) and a binding site for arsenic or antimony. Binding of metalloids stimulates ATPase activity. The crystal structure of ArsA reveals that both NBSs and the metal-binding site are located at the interface between two homologous domains. A short stretch of residues connecting the metal-binding site to the NBSs provides a signal transduction pathway that conveys information on metal occupancy to the ATP hydrolysis sites. Based on these structural features, we propose that the metal-binding site is involved directly in the process of vectorial translocation of arsenite or antimonite across the membrane. The relative positions of the NBS and the inferred mechanism of allosteric activation of ArsA provide a useful model for the interaction of the catalytic domains in other transport ATPases.
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201, USA.
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Radaev
authors.forename: B P
authors.initials: BP
authors.lastname: Rosen
authors.forename: D L
authors.initials: DL
authors.lastname: Gatti
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000495:Allosteric Site; D000595:Amino Acid Sequence; D053501:Arsenite Transporting ATPases; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D016623:Ion Pumps; D019216:Metals, Heavy / Q000378:metabolism*; D008958:Models, Molecular; D009097:Multienzyme Complexes; D009711:Nucleotides / Q000378:metabolism; D011487:Protein Conformation; D015398:Signal Transduction
chemical_list: D016623:Ion Pumps; D019216:Metals, Heavy; D009097:Multienzyme Complexes; D009711:Nucleotides; D000251:Adenosine Triphosphatases; D053501:Arsenite Transporting ATPases