Читать книгу Snyder and Champness Molecular Genetics of Bacteria - Tina M. Henkin - Страница 155

Rifamycin and its more commonly used derivative, rifampin, block transcription by binding to the β subunit of RNA polymerase and specifically blocking the initiation of RNA synthesis. The antibiotic binds in the active-site channel of RNA polymerase and limits growth of the RNA chain to a few nucleotides. The property of blocking only transcription initiation has made these antibiotics very useful in the study of transcription. For example, they have been used to analyze the steps in initiation of RNA synthesis and to study the stability of RNA in the cell. These antibiotics are useful therapeutic agents in the treatment of tuberculosis and other difficult-to-treat bacterial infections because they inhibit the RNA polymerases of essentially all types of bacteria, but not the RNA polymerases of eukaryotes, so they are not toxic to humans and animals. Accordingly, many derivatives have been made from them.

In rifampin-resistant mutants, one or more amino acids in the β subunit of RNA polymerase lining the active-site channel have been changed so that rifampin can no longer bind but the RNA polymerase still functions. Chromosomal mutations that confer resistance to rifampin are fairly common and have limited the usefulness of these antibiotics somewhat.