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Microarray-based experiments revealed that thyroid hormone triiodothyronine (T3) enhanced the binding of Cy5-labeled ATP on heat shock protein 90 (Hsp90). By molecular docking experiments with T3 on Hsp90, we identified a T3 binding site (TBS) near the ATP binding site on Hsp90. A synthetic peptide encoding RIKEIVKKHSQFIGYPITLFVEKE derived from the TBS on Hsp90 showed, in MST experiments, the binding of T3 at an EC 50 of 50 μM. The binding motif can influence the activity of Hsp90 by hindering ATP accessibility or the release of ADP.

Triiodothyronine Acts as a Smart Influencer on Hsp90 via a Triiodothyronine Binding Site