10MB
Open1 Eco-ePEC: Cryo-EM structure of Eco RNAP his-elemental paused elongation complex with an open active site (open TL, SI3 and RH-FL)
Summary for 10MB
| Entry DOI | 10.2210/pdb10mb/pdb |
| EMDB information | 75280 |
| Descriptor | DNA, ZINC ION, DNA-directed RNA polymerase subunit omega, ... (11 entities in total) |
| Functional Keywords | transcription, nucleotide addition cycle, dna/rna, transcription-dna-rna complex, transcription/dna/rna |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 8 |
| Total formula weight | 415976.78 |
| Authors | Dhingra, Y.,Darst, S.A. (deposition date: 2026-01-27, release date: 2026-04-29, Last modification date: 2026-07-15) |
| Primary citation | Dhingra, Y.,Landick, R.,Campbell, E.A.,Darst, S.A. RNA polymerase inhibitors reveal active-site motions essential for the nucleotide addition cycle. Proc.Natl.Acad.Sci.USA, 123:e2609228123-e2609228123, 2026 Cited by PubMed Abstract: The nucleotide addition cycle (NAC) of multisubunit DNA-dependent RNA polymerases (RNAPs) involves coordinated conformational changes in conserved active-site structural elements, including the trigger loop (TL). The TL is open (unfolded) in most RNAP structures but can close (fold) in substrate-bound (post- or pretranslocated) states of the RNAP, promoting catalysis. TL closure has been associated with closure of another conserved structural element, the Rim-Helices/F-loop (RH-FL), but the role of the RH-FL in the NAC is unclear. Antibiotic leads CBR9379 and AAP-SO inhibit the and RNAPs, respectively, by binding in a pocket formed by the bridge helix and RH-FL. The precise mechanism of action for these inhibitors is yet to be defined. We present cryoelectron microscopy structures showing that both compounds inhibit the RNAP NAC by preventing RH-FL closure, thereby allosterically destabilizing the closed TL. This work reveals a conserved mechanistic principle of RNAP catalysis across all domains of life and provides insight for antibiotic design. PubMed: 42378287DOI: 10.1073/pnas.2609228123 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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