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. Author manuscript; available in PMC: 2023 May 19.
Published in final edited form as: Cell Chem Biol. 2021 Nov 23;29(5):854–869.e9. doi: 10.1016/j.chembiol.2021.11.004

Figure 6. TP is a pan inhibitor of Hsp70s.

Figure 6.

(A) Dose-response curves of HCV protease inhibitors demonstrate disruption of E. coli DnaK-DnaJ-GrpE ATPase activity. (B) Denatured luciferase reactivation by human chaperones Hsc70 and DnaJA2 +/− TP (100 μM) over a time course (left) and a concentration gradient of TP (right) demonstrates dose-dependent inhibition of refolding, unlike excess BC. (C) Superposition of the SBD crystal structures of E. coli DnaK, human Hsp72 (representative for Hsc70) and a model of Mtb DnaK (Kelley et al., 2015) with NR from indicated structures. Red residues in the peptide binding cleft are conserved across all three species. Error bars represent SD (n=3). See also Figure S6.