Mercuric reductase

Fox B, CT Walsh (1982) Mercuric reductase. Purification and characterization of a transposon-encoded flavoprotein containing an oxidation-reduction active disulfide. J Biol Chem 257 2498-2503. 

Steingrube VA, RJ Wallace, LC Steele, Y Pang (1991) Mercuric reductase activity and evidence of broad-spectrum mercury resistance among clinical isolates of rapidly growing mycobacteria. Antimicrob Agents Chemother 35 819-823. 

This enzyme [EC 1.16.1.1], also known as mercuric reductase, catalyzes the reaction of Hg with NADP+ and H+ to produce and NADPH. 

Nakahara, H., J. L. Schottel, T. Yamada, Y. Miyakawa, M. Asakawa, J. Harville, and S. Silver. 1985. Mercuric reductase enzymes from Streptomyces species and group B Streptococcus. J. Gen. Microbiol. 131 1053-1059. 

Olson, G. J., F. D. Porter, J. Rubinstein, and S. Silver. 1982. Mercuric reductase from a mercury-volatilizing strain of Thiobacillus ferrooxidans. J. Bacteriol. 151 (3) 1230-1236. 

Another flavoprotein constructed on the glutathione reductase pattern is the bacterial plasmid-encoded mercuric reductase which reduces the highly toxic Hg2+ to volatile elemental mercury, Hg°. A reducible... 

A variation is observed for E. coli thioredoxin reductase. The reducible disulfide and the NADPH binding site are both on the same side of the flavin rather than on opposite sides as in Fig. 15-12.190/259 Mercuric reductase also uses NADPH as the reductant transferring the 4S hydrogen. The Hg2+ presumably binds to a sulfur atom of the reduced disulfide loop and there undergoes reduction. The observed geometry of the active site is correct for this mechanism. 

Mercapturic acid 550s Mercuric reductase 787 Mercury 317... 

Bacterial mercuric reductase is a unique metal-detoxification biocatalyst, reducing mercury(II) salts to the metal. The enzyme contains flavin adenine dinucleotide, a reducible active site disulfide (Cys 135, Cys i4o), and a C-terminal pair of cysteines (Cys 553, Cys 559). Mutagenesis studies have shown that all four cysteines are required for efficient mercury(II) reduction. Mercury Lm-EXAFS studies for mercury(II) bound to both the wild-type enzyme and a very low-activity C-terminal double-alanine mutant (Cys 135, Cys uo, Ala 553, Ala 559) suggest the formation of an Hg(Cys)2 complex in each case (39). The Hg—S distances obtained were 2.31 A and are consistent with the correlation of bond length with coordination number presented above. Thus, no evidence was obtained for coordination of mercury(II) by all four active-site cysteines in the wild-type mercuric reductase. However, these studies do not define the full extent of the catalytic mechanism for mercury(II) reduction, and it is possible that a three- or four-coordinate Hg(Cys) complex is a key intermediate in the process. 

Miller, S University of California-SF San Francisco, CA Cause and effect of dimer asymmetry in mercuric reductase. NIGMS... 

Brown, N.L., S.J. Ford, R.D. Pridmore, and D.C. Fritzinger. 1983. Nucleotide sequence of a gene fi om the Pseudomonas transposon Tn501 encoding mercuric reductase. Biochemistry 22 (17) 4089-4095. 

FDA (Center for Drug Evaluation and Research). 1999. List of Drug and Pood that Contain Intentionally Introduced Mercury Compounds. Updated November 17, 1999. Online. Available http //www.fda.gov/cder/fdama/mercury300.htm Fox, B., and C.T Walsh. 1982. Mercuric reductase. Purification and characterization of a transposon-encoded flavoprotein containing an oxidation-reduction-active disulfide. J. Biol. Chem. 257(5) 2498-2503. 

Fox, B.S., and C.T. Walsh. 1983. Mercuric reductase Homology to glutathione reductase and lipoamide dehydrogenase. lodoacetamide alkylation and sequence of the active site peptide. Biochemistry 22(17) 4082-4088. 

Figure 3-7. Sequence alignment of various enzymes in the flavopro-tein disulfide oxidoreductase family. The sequences of the NADP4-dependent enzymes are the glutathione reductase from E. coli (E-GR), human (H-GR), Pseudomonas aeruginosa (P-GR), mercuric reductase from Staphylococcus aureus (S-MR), P. aeruginosa Tn 501 (P-GR), and trypanothione reductase from Trypanosoma congolense (T-TR). The NAD+-dependent enzymes are dihydrolipoamide dehydrogenase from E. coli (E-DD), B. stearothermophilus (B-DD), yeast (Y-DD), and human (H-DD). Residue positions marked with an asterisk correspond to those that were targets of site-directed mutagenesis in the text.

Many bacteria are resistant to inorganic and organic mercury compounds. Mercuric reductase (MerA) is a key enzyme in the mercury detoxification pathway. MerA catalyzes the NADPH-dependent reduction of Hg to its volatile, uncharged, elemental state (Hg ). MerA is a cytosolic protein that is homologous to GR, but also has a short C-terminal extension and a long N-terminal extension not found in GR. MerA contains three pairs of cysteines one in the C-terminal extension, one in the N-terminal extension, and one in the GR-like region of the protein. The N-terminal domain binds one molecule of mercury and delivers it to the catalytic core of the protein, made up of the GR-like portion and the C-terminal extension, where it is reduced. The disulfide from... 

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