Disease relevance of arsC

• The Escherichia coli arsC gene encodes arsenate reductase (ArsC), which catalyzes the glutathione (GSH)-coupled electrochemical reduction of arsenate to the more toxic arsenite [1].
• Arsenate reductase (ArsC) from Staphylococcus aureus plasmid pI258 plays a role in bacterial heavy metal resistance and catalyzes the reduction of arsenate to arsenite [2].
• The thioredoxin-coupled arsenate reductase class is represented by Staphylococcus aureus pI258 ArsC and Bacillus subtilis ArsC [3].
• An arsenate reductase from Synechocystis sp. strain PCC 6803 exhibits a novel combination of catalytic characteristics [4].

High impact information on arsC

• While arsC, the arsenate reductase gene, contained no mutations, its expression level was increased, and the rate of arsenate reduction was increased 12-fold [5].
• LmACR2 was able to complement the arsenate-sensitive phenotype of an arsC deletion strain of Escherichia coli or an ScACR2 deletion strain of Saccharomyces cerevisiae [6].
• Analysis of grx mutants lacking one or both cysteine residues in the Cys-Pro-Tyr-Cys active site demonstrated that only the N-terminal cysteine residue is essential for arsenate reductase activity [7].
• An arsC gene with six histidine codons added to the 5' end of the gene was constructed, and the resulting ArsC enyzme was shown to be functional [8].
• The ars operon is composed of three structural genes, arsA, arsB, and arsC [9].

Chemical compound and disease context of arsC

• The ArsC arsenate reductase from Escherichia coli plasmid R773, the best characterized arsenic-modifying enzyme, has a catalytic cysteine, Cys 12, in the active site, surrounded by an arginine triad composed of Arg 60, Arg 94, and Arg 107 [10].
• Arginine 60 in the ArsC arsenate reductase of E. coli plasmid R773 determines the chemical nature of the bound As(III) product [10].

Biological context of arsC

• Although resistance required the arsC gene, the rate of reduction of arsenate to arsenite was nearly the same in cells lacking the ars operon [11].
• Instead, it appears that arsenate reduction by the Desulfovibrio strain Ben-RA is catalyzed by an arsenate reductase that is encoded by a chromosomally-borne gene shown to be homologous to the arsC gene of the Escherichia coli plasmid, R773 ars system [12].
• The rice genome contains two ACR2-like genes, OsACR2.1 and OsACR2.2, which may be involved in regulating arsenic metabolism in rice. * Here, we cloned both OsACR2 genes and expressed them in an Escherichia coli strain in which the arsC gene was deleted and in a yeast (Saccharomyces cerevisiae) strain with a disrupted ACR2 gene [13].
• Three open reading frames for genes arsA, arsB, and arsC were found [14].
• A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance [15].

Associations of arsC with chemical compounds

• Cells expressing any of those arsC genes were sensitive to arsenate [16].
• The ars operon expressed in S. lividans and the arsC gene expressed in S. noursei did not render the synthesis of undecylprodigiosin and nourseothricin, respectively, phosphate-resistant [17].
• Finally, the less well documented arsenate reductase activity of the monomeric arsenic(III) methylase, which is an S-adenosylmethionine (AdoMet)-dependent methyltransferase [3].
• This structural arrangement shows similarities with other IIB subunits but also with mammalian low molecular weight protein tyrosine phosphatases (LMW PTPase) and arsenate reductase (ArsC) [18].
• Nitrate, sulfate, selenate and fumarate cannot serve as alternative electron acceptors for the arsenate reductase [19].

Analytical, diagnostic and therapeutic context of arsC

• The essential cysteinyl residues and redox couple in arsenate reductase were identified by a combination of site-specific mutagenesis and endoprotease-digest mass spectroscopy analysis [20].

References