Organomercury lyase

Begley, T.P., A.E. Walts, and C.T. Walsh. 1986. Bacterial organomercurial lyase Overproduction, isolation, and characterization. Biochemistry 25(22) 7186-7192. 

Melnick and Parkin50 reported a functional model for mercury detoxification by organomercurial lyase MerB. The alkyl compound [HgR(Trn Bu)] (R = Me or Et) reacts with phenylthiol (PhSH) yielding [HgSPh(Tm Bu)] and RH. [HgR(W Bu)] exist as linear two-coordinate complexes in the solid state, whereas in solution a rapid equilibrium between [HgR(ic2-Tm Bu)] and [HgR(K3-Tm Bu)] occurs. 

Melnick and Parkin153 reported a functional model for mercury detoxification by organomercurial lyase MerB. The interaction of the alkyl compound [HgR(Tm Bu)] with phenylthiol has been investigated. 

Microbial demethylations, or dealkylations, of organometallic forms are important reactions in detoxification mechanisms for some metals, such as mercury and tin. Bacterial detoxification of organomercurials is well established and involves the enzyme organomercurial lyase (OL)—a product of the merB gene—that enzymatically cleaves the Hg-C bond to form Hg, which is then reduced by the enzyme mercuric reductase (MR) to the less toxic Hg(0) (Equations (4) and (5)). The high volatility of Hg(0) results in it being rapidly removed to the atmosphere. 

Metbylmercury, in turn, is decomposed abi-otically and by bacteria containing mercuric reductase and organomercurial lyase these demethylating strains of bacteria are common in the environment and have been isolated from water, sediments, soils, and the G1 tract of humans and other mammals. Other mechanisms can reduce inorganic Hg + to Hg in freshwater, with Hg production higher under anoxic conditions, in a chloride-free environment, and at pH 4.5. Metbylmercury concentrations in tissues of marine fishes can now be detected at levels >10.0p,g/kg tissue using graphite furnace sample preparation techniques and atomic absorption spectrometry. 

In the following sections, some of the approaches and applications described in this article are illustrated using three case studies from our own work. We begin with a mechanistic study of the bacterial organomercurial lyase, MerB, using a quantum chemical cluster method, followed by a QM/MM free energy simulation of the dual-specificity phosphatase, Cdc25B, and a dual QM and QM/MM study of the restriction enzyme EcoRV. 

Case Study 1 Organomercurial Lyase, MerB. In recent work, the mechanism of Hg-C bond cleavage by the bacterial enzyme organomercurial lyase (MerB) was examined using a quantum chemical cluster model (160). 

Hg to less toxic and volatile Hg, and sometimes (d) the additional enzyme organomercurial lyase, which cleaves the carbon-mercury bond in organomercurials such as phenylmercury and methylmercury (releasing benzene and methane plus Hg , the substrate for the mercuric reductase enzyme Walsh et al. 1988). 

Fig. 3. Reaction mechanism for organomercurial lyase (modified from Silver 1992, with permission). A, Reduced enzyme B, with organomercurial (R-Hg) bound to one cysteine thiol C, R-Hg bound to two thiols and Se2 attack of proton on R-group D, product Hg " bound to two cysteine thiols...

Begley TP, Walts AE, Walsh CT (1986) Mechanistic studies of a protonolytic organomercurial cleaving enzyme bacterial organomercurial lyase. Biochemistry 25 7192-7200... 

Walts AE, Walsh CT (1988) Bacterial organomercurial lyase novel enzymatic protonolysis of organostannanes. J Am Chem Soc 110 1950-1953 Wang Y, Moore M, Levinson HS, Silver S, Walsh C, Mahler I (1989) Nucleotide sequence of a chromosomal mercury resistance determinant from a Bacillus sp. with broad-spectrum mercury-resistance. J Bacteriol 171 83-92 Williams JR, Morgan A, Rouch DA, Brown NL, Lee BTO (1993) Copper-resistant enteric bacteria from United Kingdom and Australian piggeries. Appl Environ Microbiol 59 2531-2537... 

---