2a69: Difference between revisions
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'''Crystal structure of the T. Thermophilus RNA polymerase holoenzyme in complex with antibiotic rifapentin''' | '''Crystal structure of the T. Thermophilus RNA polymerase holoenzyme in complex with antibiotic rifapentin''' | ||
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[[Category: Vassylyeva, M N.]] | [[Category: Vassylyeva, M N.]] | ||
[[Category: Wakatsuki, S.]] | [[Category: Wakatsuki, S.]] | ||
[[Category: | [[Category: Antibiotic]] | ||
[[Category: | [[Category: Rifapentin]] | ||
[[Category: | [[Category: Riken structural genomics/proteomics initiative]] | ||
[[Category: | [[Category: Rna polymerase holoenzyme]] | ||
[[Category: | [[Category: Rsgi]] | ||
[[Category: | [[Category: Structural genomic]] | ||
[[Category: | [[Category: Transcription regulation]] | ||
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Revision as of 18:39, 3 May 2008
Crystal structure of the T. Thermophilus RNA polymerase holoenzyme in complex with antibiotic rifapentin
OverviewOverview
Rifamycins, the clinically important antibiotics, target bacterial RNA polymerase (RNAP). A proposed mechanism in which rifamycins sterically block the extension of nascent RNA beyond three nucleotides does not alone explain why certain RNAP mutations confer resistance to some but not other rifamycins. Here we show that unlike rifampicin and rifapentin, and contradictory to the steric model, rifabutin inhibits formation of the first and second phosphodiester bonds. We report 2.5 A resolution structures of rifabutin and rifapentin complexed with the Thermus thermophilus RNAP holoenzyme. The structures reveal functionally important distinct interactions of antibiotics with the initiation sigma factor. Strikingly, both complexes lack the catalytic Mg2+ ion observed in the apo-holoenzyme, whereas an increase in Mg2+ concentration confers resistance to rifamycins. We propose that a rifamycin-induced signal is transmitted over approximately 19 A to the RNAP active site to slow down catalysis. Based on structural predictions, we designed enzyme substitutions that apparently interrupt this allosteric signal.
About this StructureAbout this Structure
2A69 is a Protein complex structure of sequences from Thermus thermophilus. Full crystallographic information is available from OCA.
ReferenceReference
Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins., Artsimovitch I, Vassylyeva MN, Svetlov D, Svetlov V, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Tahirov TH, Vassylyev DG, Cell. 2005 Aug 12;122(3):351-63. PMID:16096056 Page seeded by OCA on Sat May 3 18:39:37 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- DNA-directed RNA polymerase
- Protein complex
- Thermus thermophilus
- Artsimovitch, I.
- Igarashi, N.
- Matsugaki, N.
- Perederina, A.
- RSGI, RIKEN Structural Genomics/Proteomics Initiative.
- Svetlov, D.
- Svetlov, V.
- Tahirov, T H.
- Vassylyev, D G.
- Vassylyeva, M N.
- Wakatsuki, S.
- Antibiotic
- Rifapentin
- Riken structural genomics/proteomics initiative
- Rna polymerase holoenzyme
- Rsgi
- Structural genomic
- Transcription regulation