title: Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center.
abstract: Rifamycin antibacterial agents inhibit bacterial RNA polymerase (RNAP) by binding to a site adjacent to the RNAP active center and preventing synthesis of RNA products >2-3 nt in length. Recently, Artsimovitch et al. [(2005) Cell 122:351-363] proposed that rifamycins function by allosteric modulation of binding of Mg(2+) to the RNAP active center and presented three lines of biochemical evidence consistent with this proposal. Here, we show that rifamycins do not affect the affinity of binding of Mg(2+) to the RNAP active center, and we reassess the three lines of biochemical evidence, obtaining results not supportive of the proposal. We conclude that rifamycins do not function by allosteric modulation of binding of Mg(2+) to the RNAP active center.
authors.affiliation: Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Feklistov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mekler
authors.forename: Qiaorong
authors.initials: Q
authors.lastname: Jiang
authors.forename: Lars F
authors.initials: LF
authors.lastname: Westblade
authors.forename: Herbert
authors.initials: H
authors.lastname: Irschik
authors.forename: Rolf
authors.initials: R
authors.lastname: Jansen
authors.forename: Arkady
authors.initials: A
authors.lastname: Mustaev
authors.forename: Seth A
authors.initials: SA
authors.lastname: Darst
authors.forename: Richard H
authors.initials: RH
authors.lastname: Ebright
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D009154:Mutation; D012294:Rifamycins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases; D008274:Magnesium
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