Title | Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Feklistov A, Mekler V, Jiang Q, Westblade LF, Irschik H, Jansen R, Mustaev A, Darst SA, Ebright RH |
Journal | Proc Natl Acad Sci U S A |
Volume | 105 |
Issue | 39 |
Pagination | 14820-5 |
Date Published | 2008 Sep 30 |
ISSN | 1091-6490 |
Keywords | Allosteric Regulation, Anti-Bacterial Agents, Binding Sites, DNA-Directed RNA Polymerases, Magnesium, Mutation, Rifamycins |
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. |
DOI | 10.1073/pnas.0802822105 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 18787125 |
Grant List | GM30717 / GM / NIGMS NIH HHS / United States GM61898 / GM / NIGMS NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States AI072766 / AI / NIAID NIH HHS / United States GM41376 / GM / NIGMS NIH HHS / United States |
Related Faculty:
Lars Westblade, Ph.D.