2ppb
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| , resolution 3.00Å | |||||||
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| Ligands: | , , , , , , , , , , , | ||||||
| Activity: | DNA-directed RNA polymerase, with EC number 2.7.7.6 | ||||||
| Related: | 2O5I, 2O5J
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the T. thermophilus RNAP polymerase elongation complex with the ntp substrate analog and antibiotic streptolydigin
OverviewOverview
The mechanism of substrate loading in multisubunit RNA polymerase is crucial for understanding the general principles of transcription yet remains hotly debated. Here we report the 3.0-A resolution structures of the Thermus thermophilus elongation complex (EC) with a non-hydrolysable substrate analogue, adenosine-5'-[(alpha,beta)-methyleno]-triphosphate (AMPcPP), and with AMPcPP plus the inhibitor streptolydigin. In the EC/AMPcPP structure, the substrate binds to the active ('insertion') site closed through refolding of the trigger loop (TL) into two alpha-helices. In contrast, the EC/AMPcPP/streptolydigin structure reveals an inactive ('preinsertion') substrate configuration stabilized by streptolydigin-induced displacement of the TL. Our structural and biochemical data suggest that refolding of the TL is vital for catalysis and have three main implications. First, despite differences in the details, the two-step preinsertion/insertion mechanism of substrate loading may be universal for all RNA polymerases. Second, freezing of the preinsertion state is an attractive target for the design of novel antibiotics. Last, the TL emerges as a prominent target whose refolding can be modulated by regulatory factors.
About this StructureAbout this Structure
2PPB is a Protein complex structure of sequences from Thermus thermophilus. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for substrate loading in bacterial RNA polymerase., Vassylyev DG, Vassylyeva MN, Zhang J, Palangat M, Artsimovitch I, Landick R, Nature. 2007 Jul 12;448(7150):163-8. Epub 2007 Jun 20. PMID:17581591
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