1ynj | pdb_00001ynj
Taq RNA polymerase-Sorangicin complex
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Overview
A combined structural, functional, and genetic approach was used to, investigate inhibition of bacterial RNA polymerase (RNAP) by sorangicin, (Sor), a macrolide polyether antibiotic. Sor lacks chemical and structural, similarity to the ansamycin rifampicin (Rif), an RNAP inhibitor widely, used to treat tuberculosis. Nevertheless, structural analysis revealed Sor, binds in the same RNAP beta subunit pocket as Rif, with almost complete, overlap of RNAP binding determinants, and functional analysis revealed, that both antibiotics inhibit transcription by directly blocking the path, of the elongating transcript at a length of 2-3 nucleotides. Genetic, analysis indicates that Rif binding is extremely sensitive to mutations, expected to change the shape of the antibiotic binding pocket, while Sor, is not. We suggest that conformational flexibility of Sor, in contrast to, the rigid conformation of Rif, allows Sor to adapt to changes in the, binding pocket. This has important implications for drug design against, rapidly mutating targets.
About this Structure
1YNJ is a Protein complex structure of sequences from Thermus aquaticus with SRN and ZN as ligands. Active as DNA-directed RNA polymerase, with EC number 2.7.7.6 Full crystallographic information is available from OCA.
Reference
Structural, functional, and genetic analysis of sorangicin inhibition of bacterial RNA polymerase., Campbell EA, Pavlova O, Zenkin N, Leon F, Irschik H, Jansen R, Severinov K, Darst SA, EMBO J. 2005 Feb 23;24(4):674-82. Epub 2005 Feb 3. PMID:15692574
Page seeded by OCA on Wed Nov 21 06:55:59 2007
