Steven Cheng

@scheng23.bsky.social

526 Followers 1211 Following

Chemistry & Chemical Biology PhD Candidate @Harvard woolab.org | Chemical Engineering @Stanford Alumnus | Small molecules 💊, PTMs (esp O-GlcNAc 🟦), RNA splicing 🧬

Figure 3. (A) Representative cryo-EM map of a stalled RNC with a tRNA in the P site, bound to IDB-001.
Inset shows a closeup of the PTC containing the IDB-001 (yellow), P-site tRNA (green), nascent
chain (salmon), rRNA (dark blue), and signal for ions and water molecules (red).

Movie poster of The Brutalist

Cartoon schematic of molecular crowbar degraders. Caption: Schematic illustration of the proposed mechanism of how a molecular crowbar induces Pin1 degradation. Binding of our agents to Pin1 brings the reactive acetyl group of the inhibitor close to Cys113. Upon formation of a covalent bond between the inhibitor to Cys113, the inhibitor-bound Cys113 acts like a molecular crowbar. It destabilizes the short helix D causing the helix to unfold and loop FG to move its position exposing hydrophobic residues such as Trp 73. Hence, our inhibitor acts as a molecular crowbar that opens up and destabilizes Pin and subsequent cellular degradation.