Abstract
The mechanism of inhibition of human RNA polymerase by four rifamycin derivatives was investigated. Derivative AF/013 (3-formyl rifamycin SV:O-n-octyloxime) with strong hydrophobic side chains prevents the polymerase from binding to DNA and also affects the size of RNA synthesized. Derivative PR/19 (3′-acetyl-1′-benzyl-2′-methylpyrrolo[3,2-c]-4-desoxy-rifamycin SV) only affects RNA synthesis when RNA polymerase has been previously incubated with the drug or when the reaction was performed at high salt concentration [0.14 M (NH4)2-SO4]. Our results suggest that these drugs exert their inhibitory actions by binding to the enzyme instead of DNA.
Keywords: (AF/013)(PR/19)
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Burgess R. R. RNA polymerase. Annu Rev Biochem. 1971;40:711–740. doi: 10.1146/annurev.bi.40.070171.003431. [DOI] [PubMed] [Google Scholar]
- Butterworth P. H., Cox R. F., Chesterton C. J. Transcription of mammalian chromatin by mammalian DNA-dependent RNA polymerases. Eur J Biochem. 1971 Nov 11;23(2):229–241. doi: 10.1111/j.1432-1033.1971.tb01613.x. [DOI] [PubMed] [Google Scholar]
- Chamberlin M. J., Ring J. Characterization of T7 specific RNA polymerase. 3. Inhibition by derivatives of rifamycin SV. Biochem Biophys Res Commun. 1972 Nov 15;49(4):1129–1136. doi: 10.1016/0006-291x(72)90330-0. [DOI] [PubMed] [Google Scholar]
- Chambon P., Ramuz M., Mandel P., Doly J. Inhibition of RNA polymerase by sodium polyethylene sulphonate. Biochim Biophys Acta. 1967 Dec 19;149(2):584–586. doi: 10.1016/0005-2787(67)90186-4. [DOI] [PubMed] [Google Scholar]
- Jones O. W., Berg P. Studies on the binding of RNA polymerase to polynucleotides. J Mol Biol. 1966 Dec 28;22(2):199–209. doi: 10.1016/0022-2836(66)90126-4. [DOI] [PubMed] [Google Scholar]
- Lindell T. J., Weinberg F., Morris P. W., Roeder R. G., Rutter W. J. Specific inhibition of nuclear RNA polymerase II by alpha-amanitin. Science. 1970 Oct 23;170(3956):447–449. doi: 10.1126/science.170.3956.447. [DOI] [PubMed] [Google Scholar]
- Meilhac M., Tysper Z., Chambon P. Animal DNA-dependent RNA polymerases. 4. Studies on inhibition by rifamycin derivatives. Eur J Biochem. 1972 Jul 13;28(2):291–300. doi: 10.1111/j.1432-1033.1972.tb01913.x. [DOI] [PubMed] [Google Scholar]
- Roeder R. G., Rutter W. J. Multiple forms of DNA-dependent RNA polymerase in eukaryotic organisms. Nature. 1969 Oct 18;224(5216):234–237. doi: 10.1038/224234a0. [DOI] [PubMed] [Google Scholar]
- Sippel A., Hartmann G. Mode of action of rafamycin on the RNA polymerase reaction. Biochim Biophys Acta. 1968 Mar 18;157(1):218–219. doi: 10.1016/0005-2787(68)90286-4. [DOI] [PubMed] [Google Scholar]
- Umezawa H., Mizuno S., Yamazaki H., Nitta K. Inhibition of DNA-dependent RNA synthesis by rifamycins. J Antibiot (Tokyo) 1968 Mar;21(3):234–236. doi: 10.7164/antibiotics.21.234. [DOI] [PubMed] [Google Scholar]
- Ward D. C., Reich E., Goldberg I. H. Base specificity in the interaction of polynucleotides with antibiotic drugs. Science. 1965 Sep 10;149(3689):1259–1263. doi: 10.1126/science.149.3689.1259. [DOI] [PubMed] [Google Scholar]
- Weaver R. F., Blatti S. P., Rutter W. J. Molecular structures of DNA-dependent RNA polymerases (II) from calf thymus and rat liver. Proc Natl Acad Sci U S A. 1971 Dec;68(12):2994–2999. doi: 10.1073/pnas.68.12.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wehrli W., Staehelin M. Actions of the rifamycins. Bacteriol Rev. 1971 Sep;35(3):290–309. doi: 10.1128/br.35.3.290-309.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]