title: Antibiotic streptolydigin requires noncatalytic Mg2+ for binding to RNA polymerase.
abstract: Multisubunit RNA polymerase, an enzyme that accomplishes transcription in all living organisms, is a potent target for antibiotics. The antibiotic streptolydigin inhibits RNA polymerase by sequestering the active center in a catalytically inactive conformation. Here, we show that binding of streptolydigin to RNA polymerase strictly depends on a noncatalytic magnesium ion which is likely chelated by the aspartate of the bridge helix of the active center. Substitutions of this aspartate may explain different sensitivities of bacterial RNA polymerases to streptolydigin. These results provide the first evidence for the role of noncatalytic magnesium ions in the functioning of RNA polymerase and suggest new routes for the modification of existing and the design of new inhibitors of transcription.
authors.affiliation: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Savva
authors.initials: S
authors.lastname: Zorov
authors.forename: Yulia
authors.initials: Y
authors.lastname: Yuzenkova
authors.forename: Vadim
authors.initials: V
authors.lastname: Nikiforov
authors.forename: Konstantin
authors.initials: K
authors.lastname: Severinov
authors.forename: Nikolay
authors.initials: N
authors.lastname: Zenkin
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D020134:Catalytic Domain; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D008274:Magnesium / Q000378:metabolism*; D019914:Taq Polymerase / Q000187:drug effects; D016963:Thermus thermophilus / Q000187:drug effects / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C100307:streptolydigin; D019914:Taq Polymerase; D012321:DNA-Directed RNA Polymerases; D008274:Magnesium