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VX-809 and bithiazoles appear to interact at different sites in the TMDs as the F337R mutant only prevented rescue with bithiazoles.
These two protected regions may correspond to binding sites for the EZH2 and EED subunits which interact at different sites on the RNA.
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Drugs interacting at different sites in the cell cycle might potentiate the therapeutic response.
We found that the 4R regions of the two GHSR1a protomers simultaneously interacted with Gαq at different sites when GHSR1a was dimerized via interactions between transmembrane helices 5 and 6 (TM-V and TM-VI).
These data demonstrate that T119M TTR is very inefficient at displacing f-V122I TTR from the cells and suggest that either f-V122I TTR and T119M TTR interact with the cells at different sites, or that the affinity of T119M TTR for the cell binding site is much lower than that of f-V122I TTR and by inference to that of V122I TTR.
What of interactions between different signals at different sites?
There is strong evidence that the NEMO dimer adopts a highly extended structure, and NEMO has been proposed to interact with a number of various proteins at different sites along its length.
JP2 interacts with phosphatidylserine, Kd ~0.5 μM, and PtdIns 3,4,5) P3 at different sites; divalent cations perturb the association.
These regional-scale factors may interact, and some may be more or less important at different sites.
That both heparan sulfate and laminin can interact with 37LRP simultaneously suggest that the two molecules bind at different sites and that there is limited (or no) allosteric communication between these sites.
Some patients were explored at different sites.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com