RNA polymerase-rifamycin. A molecular model of inhibition
Chertov, O.Iu.; Obukhov, A.N.; Lipkin, V.M.
Bioorganicheskaia Khimiia 9(5): 633-640
1983
ISSN/ISBN: 0132-3423 PMID: 6207842 Document Number: 209853
By fluorimetric titration of RNA polymerase from a rifamycin-sensitive Escherichia coli strain [Rifs] and that from a rifamycin-resistant E. coli strian [Rifr] with rifamycin, the mutant polymerase was demonstrated to bind rifamycin. A comparison of spatial structures of rifamycin and a dinucleotide fragment of RNA revealed similarity. Taking into account this structural similarity and the fact that 2 phosphodiester bonds can be formed by RNA polymerase in the presence of rifamycin, a model for the inhibition mode was proposed. According to this model, rifamycin occupies the place of 2 terminal nucleotides of synthesized, but not translocated pentanucleotide, in the transcribing complex. Asp-516 of the wild type .beta.-subunit was assumed to form a H bond with the rifamycin C(23) hybroxyl group. Based on this model, reduced cycling synthesis of tetra-, through decanucleotides by the Rifr RNA polymerase was predicted.