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Peptide deformylase (PDF) has emerged as an important antibacterial drug target. Considerable effort is being directed toward developing peptidic and non-peptidic inhibitors for this metalloprotein. In this work, the known peptidic inhibitor BB-3497 and its various ionization and tautomeric states are evaluated for their inhibition efficiency against PDF using a molecular mechanics (MM) approach as well as a mixed quantum mechanics/molecular mechanics (QM/MM) approach, with an aim to understand the interactions in the binding site. The evaluated Gibbs energies of binding with the mixed QM/MM approach are shown to have the best predictive power. The experimental pose is found to have the most negative Gibbs energy of binding, and also the smallest strain energy. A quantum mechanical evaluation of the active site reveals the requirement of strong chelation by the ligand with the metal ion. The investigated ligand chelates the metal ion through the two oxygens of its reverse hydroxamate moiety, particularly the N-O(-) oxygen, forming strong covalent bonds with the metal ion, which is penta-coordinated. In the uninhibited state, the metal ion is tetrahedrally coordinated, and hence chelation with the inhibitor is associated with an increase of the metal ion coordination. Thus, the strong binding of the ligand at the binding site is accounted for.

Arsenic (As) is a metalloid prevalent mainly in soil and water. The presence of As above permissible levels becomes toxic and detrimental to living organisms, therefore, making it a significant global concern. Humans can absorb As through drinking polluted water and consuming As-contaminated food material grown in soil having As problems. Since human beings are mobile organisms, they can use clean uncontaminated water and food found through various channels or switch from an As-contaminated area to a clean area; but plants are sessile and obtain As along with essential minerals and water through roots that make them more susceptible to arsenic poisoning and consequent stress. Arsenic and phosphorus have many similarities in terms of their physical and chemical characteristics, and they commonly compete to cause physiological anomalies in biological systems that contribute to further stress. Initial indicators of arsenic’s propensity to induce toxicity in plants are a decrease in yield and a loss in plant biomass. This is accompanied by considerable physiological alterations; including instant oxidative surge; followed by essential biomolecule oxidation. These variables ultimately result in cell permeability and an electrolyte imbalance. In addition, arsenic disturbs the nucleic acids, the transcription process, and the essential enzymes engaged with the plant system’s primary metabolic pathways. To lessen As absorption by plants, a variety of mitigation strategies have been proposed which include agronomic practices, plant breeding, genetic manipulation, computer-aided modeling, biochemical techniques, and the altering of human approaches regarding consumption and pollution, and in these ways, increased awareness may be generated. These mitigation strategies will further help in ensuring good health, food security, and environmental sustainability. This article summarises the nature of the impact of arsenic on plants, the physio-biochemical mechanisms evolved to cope with As stress, and the mitigation measures that can be employed to eliminate the negative effects of As.

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