Figure 1.
Ligand binding site similarity between COMT and InhA.
COMT is show in green, its SAM co-factor is shown in purple, and its ligand is shown in red. InhA is shown in blue, its NAD co-factor is shown in orange, and its ligand is shown in yellow. Protein structures were aligned using the SOIPPA algorithm.
Figure 2.
2D small molecule similarity between existing and potential InhA inhibitors.
The p-value of the InhA inhibitor with the highest 2D similarity score (Tanimoto coefficient) to A) entacapone and B) tolcapone is shown against a density distribution of 15,000 background scores.
Table 1.
Docking existing and potential InhA inhibitors into InhA and COMT.
Figure 3.
Binding pose analysis of entacapone with InhA.
The eHiTs predicted binding pose of entacapone is compared with that of a native InhA ligand. The native ligand is shown in yellow and entacapone is colored by element. The NAD co-factor is shown in orange. Distances between the nitrite group of entacapone and surrounding aspartic acid and glutamic acid residues are labeled.
Table 2.
Comparison of logP and logD values between existing and potential anti-tubercular drugs or pro-drugs (marked by an asterisk).
Table 3.
In vitro assay results for sensitivity of M.tuberculosis to entacapone.
Table 4.
InhA kinetic assay results for entacapone inhibition.