title: Mechanism of the ArsA ATPase.
abstract: The ArsAB ATPase confers metalloid resistance in Escherichia coli by pumping toxic anions out of the cells. This transport ATPase shares structural and perhaps mechanism features with ABC transporters. The ArsAB pump is composed of a membrane subunit that has two groups of six transmembrane segments, and the catalytic subunit, the ArsA ATPase. As is the case with many ABC transporters, ArsA has an internal repeat, each with an ATP binding domain, and is allosterically activated by substrates of the pump. The mechanism of allosteric activation of the ArsA ATPase has been elucidated at the molecular level. Binding of the activator produces a conformational change that forms a tight interface of the nucleotide binding domains. In the rate-limiting step in the overall reaction, the enzyme undergoes a slow conformational change. The allosteric activator accelerates catalysis by increasing the velocity of this rate-limiting step. We postulate that similar conformational changes may be rate-limiting in the mechanism of ABC transporters.
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, MI 48201, USA. brosen@med.wayne.edu
authors.forename: B P
authors.initials: BP
authors.lastname: Rosen
authors.forename: H
authors.initials: H
authors.lastname: Bhattacharjee
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.forename: A R
authors.initials: AR
authors.lastname: Walmsley
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000495:Allosteric Site; D000595:Amino Acid Sequence; D053501:Arsenite Transporting ATPases; D002384:Catalysis; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology*; D016623:Ion Pumps; D007700:Kinetics; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D016297:Mutagenesis, Site-Directed; D013439:Sulfhydryl Reagents
chemical_list: D016623:Ion Pumps; D009097:Multienzyme Complexes; D013439:Sulfhydryl Reagents; D000251:Adenosine Triphosphatases; D053501:Arsenite Transporting ATPases