Mer operon

Some metals can be converted to a less toxic form through enzyme detoxification. The most well-described example of this mechanism is the mercury resistance system, which occurs in S. aureus,43 Bacillus sp.,44 E. coli,45 Streptomyces lividans,46 and Thiobacillus ferrooxidans 47 The mer operon in these bacteria includes two different metal resistance mechanisms.48 MerA employs an enzyme detoxification approach as it encodes a mercury reductase, which converts the divalent mercury cation into elemental mercury 49 Elemental mercury is more stable and less toxic than the divalent cation. Other genes in the operon encode membrane proteins that are involved in the active transport of elemental mercury out of the cell.50 52... 

Inoue, C., Sugawara, K., and Kusano, T., Thiobacillus ferrooxidans mer operon Sequence analysis of the promoter and adjacent genes, Gene, 96 (1), 115-120, 1990. 

One of the first metalloregulatory proteins to be characterized extensively is the prokaryotic MerR transcription factor (1, 6, 7), which acts either as a repressor (apo-protein) or an activator (holo-protein) of the mer operon encoding mercury resistance proteins (Fig. Ic). The —35 and —10 sequence elements of the mer promoter, binding sites for the RNA polymerase initiation complex, are separated by an unusually long distance that results in poor constitutive transcription. Apo-MerR binds to the DNA between these sequences and bends the DNA, which results in a slight increase in repression on the suboptimal promoter. It also recruits the RNA polymerase to the transcription start site where it waits in a stalled complex. Upon binding of... 

Champier L, Duarte V, Michaud-Soret I, Coves 1. Characterization of the MerD protein from Ralstonia metallidurans CH34 A possible role in bacterial mercury resistance by switching off the induction of the mer operon. Mol. Microbiol. 2004 52 1475-1485. 

Arrangement of genes in mer operon of a gram negative bacterium (adapted from Figure 1, Reference 14). 

Osborn AM, Bruce KD, Strike P and Ritchie DA. (1997) Distribution, diversity and evolution of the bacterial mercury resistance (mer) operon. FEMS Microbiol Rev 19 239-262. 

Our second example is MerR, the protein that regulates the expression of the mer operon. Both O Halloran and Walsh predicted that MerR contained the rare Hg(SR)3 binding site (24, 25). Comparison of the spectroscopic features of MerR to those of our designed peptides is informative MerR has a Hg-S distance of 2.43 A (24) UV maxima at 240 nm (e= 16,620), 260 nm (s = 11,150) and 290 nm (e = 4,120) (26) vq and t values 1.18 GHz and 0.25 (23) and a Hg NMR chemical shift of -106 ppm (27). Comparison to the corresponding values in Tables II and III for our peptides leaves little doubt that Hg(II) is bound in a slightly distorted trigonal planar environment by three cysteinyl side chains. 

D structure is assumed to be similar to a domain of human metallothionein. The MerR regulatory protein is encoded by the mer operon of Tn507 (5) and is highly specific for Hg in its biological response. The amino acid sequence is known,... 

The expression of proteins involved in Hg(II) detoxification is regulated by the MerR protein. The MerR protein is always bound as a dimer adjacent to the RNA polymerase binding site of the mer gene. In the absence of Hg, MerR holds the DNA in a conformation so that the RNA polymerase binding is blocked and transcription cannot occur. When the mercury binds to MerR, it changes the conformation of the MerR protein-DNA complex and allows RNA polymerase to bind and transcribe the mer operon, creating mRNA for the series of enzymes that carry out mercury resistance. 

After the transport system genes, the merA gene encodes the large subunits of the dimeric protein mercuric reductase. Schiering et al. (1991) solved the crystal structure for the mercuric reductase protein from the Bacillus mer operon (see Sect. B.I.3). The structure (Fig. 2), as anticipated, is very similar to that of the homologous human protein glutathione reductase. The dimer subunits are related by a twofold rotational axis, and... 

In the absence of Hg(II), the transcription and synthesis of these Hg detoxification enzymes is inhibited by a regulatory protein, called merR, that binds to a specific location in the mer operon, the section of DNA coding for mercury resistance. When Hg(il) is present, it binds to three Cys residues of the merR protein. This causes a conformational change in both the protein and in the DNA to which it is bound that leads to transcription of the lyase and reductase. In this way, these proteins are only produced when required. ... 

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