4MQ9

Crystal structure of Thermus thermophilus RNA polymerase holoenzyme in complex with GE23077

Summary for 4MQ9

• Entry DOI: 10.2210/pdb4mq9/pdb
• Related PRD ID: PRD_001181
• Descriptor: DNA-directed RNA polymerase subunit alpha, DNA-directed RNA polymerase subunit beta, DNA-directed RNA polymerase subunit beta', ... (10 entities in total)
• Functional Keywords: dna-directed rna polymerase, transcription, transferase-antibiotic complex, transferase/antibiotic
• Biological source: Thermus thermophilus; More
• Cellular location: Cytoplasm (By similarity): Q5SKW1
• Total number of polymer chains: 7
• Total formula weight: 429585.67

Authors

Ho, M.X.,Arnold, E.,Ebright, R.H.,Zhang, Y.,Tuske, S. (deposition date: 2013-09-16, release date: 2014-05-07, Last modification date: 2023-09-20)

Primary citation

Zhang, Y.,Degen, D.,Ho, M.X.,Sineva, E.,Ebright, K.Y.,Ebright, Y.W.,Mekler, V.,Vahedian-Movahed, H.,Feng, Y.,Yin, R.,Tuske, S.,Irschik, H.,Jansen, R.,Maffioli, S.,Donadio, S.,Arnold, E.,Ebright, R.H.
GE23077 binds to the RNA polymerase 'i' and 'i+1' sites and prevents the binding of initiating nucleotides.
Elife, 3:e02450-e02450, 2014

PubMed Abstract: Using a combination of genetic, biochemical, and structural approaches, we show that the cyclic-peptide antibiotic GE23077 (GE) binds directly to the bacterial RNA polymerase (RNAP) active-center 'i' and 'i+1' nucleotide binding sites, preventing the binding of initiating nucleotides, and thereby preventing transcription initiation. The target-based resistance spectrum for GE is unusually small, reflecting the fact that the GE binding site on RNAP includes residues of the RNAP active center that cannot be substituted without loss of RNAP activity. The GE binding site on RNAP is different from the rifamycin binding site. Accordingly, GE and rifamycins do not exhibit cross-resistance, and GE and a rifamycin can bind simultaneously to RNAP. The GE binding site on RNAP is immediately adjacent to the rifamycin binding site. Accordingly, covalent linkage of GE to a rifamycin provides a bipartite inhibitor having very high potency and very low susceptibility to target-based resistance. DOI: http://dx.doi.org/10.7554/eLife.02450.001.

PubMed: 24755292

Experimental method

X-RAY DIFFRACTION (3.35 Å)