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. Author manuscript; available in PMC: 2013 Jul 1.
Published in final edited form as: Nat Commun. 2013;4:1332. doi: 10.1038/ncomms2320

Fig. 1. Ebselen inhibits inositol monophosphatase in vitro.

Fig. 1

(a) Chemical structures. For the ebselen conjugate, R is glutathione or another ebselen molecule. (b) Concentration–inhibition relationships for ebselen and known inhibitors of IMPase. Assay used expressed human IMPase. (c) Concentration–inhibition relationships for ebselen on glycogen synthase kinase 3ß. (d,e) Effect of ebselen on the enzyme kinetics of IMPase shown as a Michaelis-Menten plot (d) or a Lineweaver-Burk plot (e). (f) Effect of dilution on inhibition of IMPase by ebselen (20 μM before and 0.2 μM after dilution). (g) Effect of recovery time after dilution on inhibition of IMPase by ebselen. (h) Mass spectroscopy under mild denaturing and non-denaturing conditions of IMPase incubated with ebselen or L-690,330 (100 μM each). (i-k) Effect of mutation cysteine-218 to alanine on inhibition of IMPase by ebselen assessed by concentration-inhibition curves (i), Michaelis-Menton kinetics (ebselen 50 μM) (j) and Vmax (k). Analyzed by a pre-planned t-test, n=6. (l) Concentration-response relationships for the sulfur analogue of ebselen and dibenzyldiselenide on IMPase. (m,n) Effect of disulfide reducing agents on inhibition of IMPase by ebselen (50 μM) with either post-incubation with glutathione (GSH, 1 mM) or dithiothreitol (50 mM) (m) or pre-incubation with 5 mM and 250 mM, respectively (n). All error bars represent standard error of the means.