3CQZ

Crystal structure of 10 subunit RNA polymerase II in complex with the inhibitor alpha-amanitin

Summary for 3CQZ

• Entry DOI: 10.2210/pdb3cqz/pdb
• Related: 1K83 2VUM
• Related PRD ID: PRD_000201
• Descriptor: DNA-DIRECTED RNA POLYMERASE II SUBUNIT RPB1, DNA-DIRECTED RNA POLYMERASES I, II, AND III SUBUNIT RPABC4, ALPHA-AMANITIN, ... (13 entities in total)
• Functional Keywords: transcription-toxin complex, alpha amanitin, toxin, inhibitor, polymerase, transferase, dna binding, zinc-finger, phosphoprotein, transcription, transcription/toxin
• Biological source: SACCHAROMYCES CEREVISIAE (BREWER'S YEAST, LAGER BEER YEAST, YEAST); More
• Cellular location: Nucleus: P04050 P08518 P16370 P20434 P20436 P27999 P38902; Nucleus, nucleolus: P40422 P22139; Cytoplasm: P20435
• Total number of polymer chains: 11
• Total formula weight: 471088.25

Authors

Kaplan, C.D.,Larsson, K.-M.,Kornberg, R.D. (deposition date: 2008-04-03, release date: 2008-07-22, Last modification date: 2023-08-30)

Primary citation

Kaplan, C.D.,Larsson, K.M.,Kornberg, R.D.
The RNA Polymerase II Trigger Loop Functions in Substrate Selection and is Directly Targeted by Alpha-Amanitin.
Mol.Cell, 30:547-, 2008

PubMed Abstract: Structural, biochemical, and genetic studies have led to proposals that a mobile element of multisubunit RNA polymerases, the Trigger Loop (TL), plays a critical role in catalysis and can be targeted by antibiotic inhibitors. Here we present evidence that the Saccharomyces cerevisiae RNA Polymerase II (Pol II) TL participates in substrate selection. Amino acid substitutions within the Pol II TL preferentially alter substrate usage and enzyme fidelity, as does inhibition of transcription by alpha-amanitin. Finally, substitution of His1085 in the TL specifically renders Pol II highly resistant to alpha-amanitin, indicating a functional interaction between His1085 and alpha-amanitin that is supported by rerefinement of an alpha-amanitin-Pol II crystal structure. We propose that alpha-amanitin-inhibited Pol II elongation, which is slow and exhibits reduced substrate selectivity, results from direct alpha-amanitin interference with the TL.

PubMed: 18538653
DOI: 10.1016/J.MOLCEL.2008.04.023

Experimental method

X-RAY DIFFRACTION (2.8 Å)