2ppb: Difference between revisions

Revision as of 13:34, 4 May 2008

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 Page seeded by OCA on Sun May 4 13:34:46 2008

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OCA

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 [[Image:2ppb.gif|left|200px]]
- {{Structure
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-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
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-|DOMAIN=
+{{STRUCTURE_2ppb|  PDB=2ppb  |  SCENE=  }}
-|RELATEDENTRY=[[2o5i|2O5I]], [[2o5j|2O5J]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ppb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ppb OCA], [http://www.ebi.ac.uk/pdbsum/2ppb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ppb RCSB]</span>
-}}
 '''Crystal structure of the T. thermophilus RNAP polymerase elongation complex with the ntp substrate analog and antibiotic streptolydigin'''
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 [[Category: Vassylyev, D G.]]
 [[Category: Vassylyeva, M N.]]
-[[Category: antibiotic streptolydigin]]
+[[Category: Antibiotic streptolydigin]]
-[[Category: elongation complex]]
+[[Category: Elongation complex]]
-[[Category: non-template dna]]
+[[Category: Non-template dna]]
-[[Category: ntp substrate]]
+[[Category: Ntp substrate]]
-[[Category: rna polymerase]]
+[[Category: Rna polymerase]]
-[[Category: rna transcript]]
+[[Category: Rna transcript]]
-[[Category: template dna]]
+[[Category: Template dna]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 13:34:46 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:39:01 2008''