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Reposted by Yukti Dhingra

The Rockefeller University @rockefeller.edu · 10/08/2026

A new @pnas.org paper from Elizabeth Campbell and Seth Darst solves a longstanding mystery about how a class of antibiotics works and simultaneously reveals a key structural mechanism behind one of biology's most important enzymes: RNA polymerase. 🔗: bit.ly/45jaPV8

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Yukti Dhingra @yuktidhingra.bsky.social · 05/07/2026

Closure of RH-FL stabilizes the folded TL state via interactions between FL and TL, promoting catalysis. TL and RH-FL are structurally conserved across multi-subunit RNA polymerases from bacteria to humans, suggesting a conserved mechanism of conformational cycling across all domains of life. 4/4

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Yukti Dhingra @yuktidhingra.bsky.social · 05/07/2026

We show that previously known inhibitors of nucleotide addition, CBR and AAP, inhibit Eco and Mtb RNAPs, respectively, by blocking RH-FL closure. This reveals their uncharacterized mechanism of action and indicates that RH-FL closure is a critical step during nucleotide addition. 3/4

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Yukti Dhingra @yuktidhingra.bsky.social · 05/07/2026

The trigger loop (TL) is a key domain that folds/unfolds during each round of nucleotide addition. Folded TL orients the active-site, triggering catalysis. We find that another conserved element, the rim helices/F-loop (RH-FL), undergoes a rotation, closing/opening in concert with TL movements. 2/4

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Yukti Dhingra @yuktidhingra.bsky.social · 05/07/2026

Happy to share the first paper from my postdoc in the Darst and Campbell labs! 🧵 www.pnas.org/doi/full/10.... We used cryo-EM and allosteric inhibitors as mechanistic probes to visualize conformational landscapes of E. coli and M. tuberculosis RNA polymerases during nucleotide addition. 1/4

pnas.org

RNA polymerase inhibitors reveal active-site motions essential for the nucleotide addition cycle | PNAS

The nucleotide addition cycle (NAC) of multisubunit DNA-dependent RNA polymerases (RNAPs) involves coordinated conformational changes in conserved ...

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Reposted by Yukti Dhingra

Dipa Sashital @dsashital.bsky.social · 23/10/2023

We had a joint Sashital/Underbakke lab party to celebrate Yukti and Tania's new positions on a beautiful fall day! Also, I'm new to this app and don't know how to tag people yet!

Food, some healthy, mostly with a lot of butter

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