Molecular docking studies of dithiocarbamates compounds interactions with jack-bean urease

Molecular docking studies concerning the inclusion of dithiocarbamates compounds inside the jack-bean urease enzyme (JBU) are reported. The compounds are dimethyldithiocarbamate (MDTC), diethyldithiocarbamate (EDTC) and pyrrolidinedithiocarbamate (PDTC) and they present inhibitory activity against urease, justifying the structural investigation. Interaction energies of each dithiocarbamate inside the distinct enzyme domains are calculated and the active sites for the inhibitors are determined. The lowest electrostatic intermolecular energy (ΔE) for every compound was obtained within the C-terminal (αβ)8 domain containing the Tyr442 residue, originally corresponding to the enzymatic catalytic site. EDTC and PDTC compounds have similar ΔE and MDTC has a comparatively higher ΔE. It was observed that the stability of inclusion increases with the carbon chain of the molecules and from the ΔE perspective the relative inhibitors efficiencies are in order PDTC ≈ EDTC > MDTC. However, interactions of the dithiocarbamates with water molecules allowed determining a precise order of activity as EDTC > PDTC > MDTC. Data are supplied in this article.

Jack-bean urease (JBU) structure and the best dithiocarbamates (DTC's) conformations in each enzymatic domain: Molecular Docking calculations show the DTC's acting in the domain a involving the amino acids residues 402-701 and 762-840 of JBU.