Table 1.

The slow-onset inhibition constants (K_i*) and the Gibbs free energy values (ΔG). The DADMe-ImmA inhibitors are the mimics of the late dissociative transition state in which the distance between C1’of thioribose and N9 of adenine of the MTA is elongated. All these transition state analogues exhibited slow-onset inhibition and they diffuse out of MTAN very slowly. The top four inhibitors are novel inhibitors particularly designed for this study. The lower four inhibitors were cocrystallized with S. enterica MTAN and the corresponding structures were determined in this study. The ΔΔG values were determined by using methylthio-DADMe-ImmA as a reference.

Inhibitor	Ki* (pM)	ΔG (kcal mol−1 )	ΔΔG (kcal mol−1)
2-Hydroxyethylthio-DADMe-ImmA	11.0 ± 2.2	−14.9 ± 0.1	0.5
3-Hydroxypropylthio-DADMe-ImmA	7.0 ± 2.3	−15.2 ± 0.2	0.2
4-Hydroxybutylthio-DADMe-ImmA	14.8 ± 2.7	−14.8 ± 0.1	0.6
2-(2-hydroxyethoxy)ethylthio-DADMe-ImmA Aka diethyleneglycolthio-DADMe-ImmA	5.0 ± 0.7	−15.4 ± 0.1	0
Homocysteine-DADMe-ImmA	69.0 ± 12.1	−13.9 ± 0.1	1.5
Methylthio-DADMe-ImmA	5.0 ± 0.4	−15.4 ± 0.1	0
Butylthio-DADMe-ImmA	1.5 ± 0.4	−16.1 ± 0.2	−0.7