Syma Khalid
sykhalid.bsky.social
Prof of Computational Microbiology. Oxford Biochemistry & St Anne’s College. Bacterial Cell Envelopes. LFC fan 🌈
👤 Joined on 04 September 2023
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- 04 Eyl 2023, 12:55
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@sykhalid.bsky.social - 09 Kas 2023, 21:43
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We then performed an AF2-based screen on other class A GPCRs and found that 13 shared an identical residue at position 6.52 and 187 at position 5.47, so this kind of hydrophobic levering mechanism might have applicability beyond GPR84...
Show PostValidation work using cell-based assays and more sims followed. My personal highlight was the fact that the Russell group were able to design a ligand library that used substituents with different van der Waals radii to exploit the L336 lever as a way to modify bias. Check out the level of control!
Show PostIt turns out that in the absence of a G-protein binding partner, the -CF3 group on the ligand wedges between TM5 and TM6 and forces them apart. The hydrophobic residues can also act as a lever that twists TM6 outwards and "unplugs" the residue Y332 (6.48) from its H-bond network…
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