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N Korzheva

Publications and source records attributed to N Korzheva.

4 recordsLinked to original sources
PubMed2001

Structural mechanism for rifampicin inhibition of bacterial rna polymerase.

Rifampicin (Rif) is one of the most potent and broad spectrum antibiotics against bacterial pathogens and is a key component of anti-tuberculosis therapy, stemming from its inhibition of the bacterial RNA polymerase (RNAP). We determined the crystal structure of Thermus aquaticus core RNAP complexed with Rif. The inhibitor binds in a pocket of the RNAP beta subunit deep within the DNA/RNA channel, but more than 12 A away from the active site. The structure, combined with biochemical results, explains the effects of Rif on RNAP function and indicates that the inhibitor acts by directly blocking the path of the elongating RNA when the transcript becomes 2 to 3 nt in length.

Amino Acid Sequence↗
PubMed2001

Transcription elongation complex: structure and function.

Our understanding of the mechanisms of transcription has been greatly advanced by recent determination of the X-ray structure of bacterial RNA polymerase. Using crosslinking approaches, extensive mapping of DNA and RNA contacts onto this structure allowed tracking of the path of nucleic acids through the transcription elongation complex. The resulting structural model of the transcription elongation complex is linked to the functional one, which is based on numerous data accumulated during previous studies of RNA synthesis. An integrated structure-function model allows the rational explanation of termination and pausing and provides new insights into the mechanisms of transcription.

DNA↗
PubMed2000

A structural model of transcription elongation.

The path of the nucleic acids through a transcription elongation complex was tracked by mapping cross-links between bacterial RNA polymerase (RNAP) and transcript RNA or template DNA onto the x-ray crystal structure. In the resulting model, the downstream duplex DNA is nestled in a trough formed by the beta' subunit and enclosed on top by the beta subunit. In the RNAP channel, the RNA/DNA hybrid extends from the enzyme active site, along a region of the beta subunit harboring rifampicin resistance mutations, to the beta' subunit "rudder." The single-stranded RNA is then extruded through another channel formed by the beta-subunit flap domain. The model provides insight into the functional properties of the transcription complex.

Binding Sites↗