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Role of the Substrate Specificity-Defining Residues of Human SIRT5 in Modulating the Structural Stability and Inhibitory Features of the Enzyme

Fig 9

Structure of EX527 and its Effects on SIRT5 Variant Catalyzed Reactions.

(A) Structure of EX527. (B) Relative activities of SIRT5 variants in the absence and presence of 50 μM EX527. (C) Dose-response of SIRT1 deacetylase activity in the presence of increasing concentration of EX527 (from 0 to 40 μM). (D) Dose-response of SIRT5 Y102A/R105I deacetylase activity in the presence of increasing concentration of EX527 (from 0 to 200 μM). For (C) and (D), the solid smooth lines represent the best fit of the data for the IC50 of EX527 against SIRT1 and SIRT5 Y102A/R105I as being equal to 0.9 ± 0.2 μM and 21.7 ± 1.0 μM, respectively.

Fig 9

doi: https://doi.org/10.1371/journal.pone.0152467.g009