Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center.
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.
Feklistov
Andrey
A
Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Mekler
Vladimir
V
Jiang
Qiaorong
Q
Westblade
Lars F
LF
Irschik
Herbert
H
Jansen
Rolf
R
Mustaev
Arkady
A
Darst
Seth A
SA
Ebright
Richard H
RH
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*
D000900:Anti-Bacterial Agents; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases; D008274:Magnesium
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