Rational Drug Designing Strategies and Inhibitor Optimization: Anthrax Lethal Toxin Factor

Anthrax toxin protein protective antigen, edema factor and lethal factor are secreted by Bacillus anthracis bacteria causes several adverse effects on human as well as on ruminant animals and considered as serious biological weapons. Lethal toxin protein (combination of lethal factor and protective antigen) is highly lethal to the host and responsible for the disruption of signalling pathways, cell destruction, and circulatory shock. 1YQY is one of the crystal structures of lethal toxin protein. It has two domains - Anthrax_M_tox and ATLF where the hydroxymate as well as Zn cofactor are attached. Known inhibitor of the protein 1YQY was identified and downloaded from pubchem. Interaction of the inhibitors with the protein was examined through in silico docking approach with AutoDock 3.0.5 and Hex. Some of the inhibitors apparently interact with several-conserved residue in the cofactor-binding site. The docking work suggests virtual derivatives of the predicted inhibitor that can improve hydrogen bond interaction between inhibitor and protein. From structural and docking analyses, it is hypothesized that 1YQY protein interacts with azelastine molecule shows the lowest docking energy in AutoDock software