title: The use of divalent metal ions by type II topoisomerases.
abstract: Type II topoisomerases are essential enzymes that regulate DNA under- and overwinding and remove knots and tangles from the genetic material. In order to carry out their critical physiological functions, these enzymes utilize a double-stranded DNA passage mechanism that requires them to generate a transient double-stranded break. Consequently, while necessary for cell survival, type II topoisomerases also have the capacity to fragment the genome. This feature of the prokaryotic and eukaryotic enzymes, respectively, is exploited to treat a variety of bacterial infections and cancers in humans. All type II topoisomerases require divalent metal ions for catalytic function. These metal ions function in two separate active sites and are necessary for the ATPase and DNA cleavage/ligation activities of the enzymes. ATPase activity is required for the strand passage process and utilizes the metal-dependent binding and hydrolysis of ATP to drive structural rearrangements in the protein. Both the DNA cleavage and ligation activities of type II topoisomerases require divalent metal ions and appear to utilize a novel variant of the canonical two-metal-ion phosphotransferase/hydrolase mechanism to facilitate these reactions. This article will focus primarily on eukaryotic type II topoisomerases and the roles of metal ions in the catalytic functions of these enzymes.
authors: Department of Pharmaceutical Sciences, Lipscomb University College of Pharmacy, Nashville, TN 37204-3951, USA.
authors: Joseph E
authors: JE
authors: Deweese
authors: Neil
authors: N
authors: Osheroff
mesh_terms: D055162:Biocatalysis; D002413:Cations, Divalent / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological
chemical_list: D002413:Cations, Divalent; D004247:DNA; D004250:DNA Topoisomerases, Type II