Executive Summary : | Organomercurials (RHg+), particularly methylmercury (MeHg+) and ethylmercury (EtHg+), are highly toxic and neurotoxic environmental pollutants that accumulate in the brain and damage the central nervous system. The development of a smart system to detoxify these toxic organomercurials is crucial. In nature, mercury-resistant bacteria have mer operons that detoxify various organomercurials with the help of a series of mer proteins, including organomercurial lyase MerB, which catalyzes protolytic Hg-C bond cleavage and produces less toxic Hg2+ and volatile RH. Another mercury-reducing bacterial enzyme called mercuric ion reductase (MerA) uses the inorganic mercury Hg2+ to reduce it to less toxic elemental mercury, Hg(0), which diffuses out of the bacteria. Sulfate-reducing bacteria have evolved their Hg-resistant properties through converting RHg+ to biologically inert mercury sulfide (HgS). The active site of MerB consists of a catalytic triad of cysteine residues, aspartic acid (Asp-99) residues, and other conserved N- and O-containing residues. However, the role of these residues on the cleavage of Hg-C bond or the transfer of the product Hg2+ from MerB to MerA is unknown. Developing smart synthetic small molecules and functionalized smart materials for efficient cleavage of Hg-C bond of various organomercurials under physiologically and environmentally relevant conditions is essential for the development of antidotes and the removal of mercury compounds from ground water. This proposal addresses several points, including the efficiency of enzymatic protolytic cleavage of Hg-C bond, the role of conserved N- and O-containing residues, the slower reactivity of Ser-containing MerB2 variants, and the smooth transfer of the product Hg2+ from MerB to MerA for further reduction to Hg0. |