4MEY

Crystal structure of Escherichia coli RNA polymerase holoenzyme

Summary for 4MEY

• Entry DOI: 10.2210/pdb4mey/pdb
• Related: 4MEX
• Descriptor: DNA-directed RNA polymerase subunit alpha, DNA-directed RNA polymerase subunit beta, DNA-directed RNA polymerase subunit beta', ... (7 entities in total)
• Functional Keywords: rna polymerase, dna binding, transferase
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm (Potential): P00579
• Total number of polymer chains: 12
• Total formula weight: 923439.32

Authors

Feng, Y.,Zhang, Y.,Arnold, E.,Ebright, R.H. (deposition date: 2013-08-27, release date: 2014-05-21, Last modification date: 2024-02-28)

Primary citation

Degen, D.,Feng, Y.,Zhang, Y.,Ebright, K.Y.,Ebright, Y.W.,Gigliotti, M.,Vahedian-Movahed, H.,Mandal, S.,Talaue, M.,Connell, N.,Arnold, E.,Fenical, W.,Ebright, R.H.
Transcription inhibition by the depsipeptide antibiotic salinamide A.
Elife, 3:e02451-e02451, 2014

PubMed Abstract: We report that bacterial RNA polymerase (RNAP) is the functional cellular target of the depsipeptide antibiotic salinamide A (Sal), and we report that Sal inhibits RNAP through a novel binding site and mechanism. We show that Sal inhibits RNA synthesis in cells and that mutations that confer Sal-resistance map to RNAP genes. We show that Sal interacts with the RNAP active-center 'bridge-helix cap' comprising the 'bridge-helix N-terminal hinge', 'F-loop', and 'link region'. We show that Sal inhibits nucleotide addition in transcription initiation and elongation. We present a crystal structure that defines interactions between Sal and RNAP and effects of Sal on RNAP conformation. We propose that Sal functions by binding to the RNAP bridge-helix cap and preventing conformational changes of the bridge-helix N-terminal hinge necessary for nucleotide addition. The results provide a target for antibacterial drug discovery and a reagent to probe conformation and function of the bridge-helix N-terminal hinge.DOI: http://dx.doi.org/10.7554/eLife.02451.001.

PubMed: 24843001
DOI: 10.7554/eLife.02451

Experimental method

X-RAY DIFFRACTION (3.948 Å)