10mi

Closed Mtb-EC: Cryo-EM structure of Mtb RNAP elongation complex (substrate loading mimic) with a closed active site (closed TL and RH-FL)

spinqualitylabelsall models 10mi, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 10mi is a 8 chain structure with sequence from Escherichia coli and Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: GTP, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RPOB_MYCTU DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321] Publication Abstract from PubMed The nucleotide-addition cycle (NAC) of multi-subunit 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 pre-translocated) 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 (2) inhibit the Escherichia coli and Mycobacterium tuberculosis 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 cryo-electron 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 new insight for antibiotic design. RNA polymerase inhibitors reveal active-site motions essential for the nucleotide-addition cycle.,Dhingra Y, Landick R, Campbell EA, Darst SA bioRxiv [Preprint]. 2026 Apr 7:2026.04.06.716786. doi: , 10.64898/2026.04.06.716786. PMID:41993335 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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