In molecular biology, the ars operon is an

operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

found in several

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...

l taxon. It is required for the

detoxification Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of ...

arsenate The arsenate ion is . An arsenate (compound) is any compound that contains this ion. Arsenates are salts or esters of arsenic acid. The arsenic atom in arsenate has a valency of 5 and is also known as pentavalent arsenic or As(V). Arsenate res ...

arsenite In chemistry, an arsenite is a chemical compound containing an arsenic oxyanion where arsenic has oxidation state +3. Note that in fields that commonly deal with groundwater chemistry, arsenite is used generically to identify soluble AsIII anions. ...

, and antimonite. This system transports arsenite and antimonite out of the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

produces resistance to arsenite and antimonite. Arsenate, however, must first be reduced to arsenite before it is extruded. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. ArsC is an approximately 150-residue arsenate reductase that uses reduced

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...

(GSH) to convert arsenate to arsenite with a

redox Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

active cysteine

residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...

in the active site. ArsC forms an active quaternary

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

with GSH, arsenate, and

glutaredoxin Glutaredoxins (also known as Thioltransferase) are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. In humans this oxidation repair enzyme is also known to participate in many cellular functi ...

1 (Grx1). The three ligands must be present simultaneously for reduction to occur.

ArsA and ArsB

ArsA and ArsB form an anion-translocating ATPase. The ArsB

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

is distinguished by its overall

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...

character, in keeping with its role as a membrane-associated channel. Sequence analysis reveals the presence of 13 putative transmembrane (TM) regions.

ArsC

The arsC protein structure has been solved. It belongs to the

thioredoxin Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by ''TXN'' and '' TXN2'' genes. Loss-of-fu ...

superfamily fold which is defined by a

beta-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a ge ...

core surrounded by

alpha-helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...

. The active cysteine

of ArsC is located in the loop between the first beta-strand and the first helix, which is also conserved in the Spx protein and its homologues. The arsC family also comprises the Spx

s which are

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

bacterial Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were amon ...

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

s that regulate the

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

of multiple

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s in response to disulphide

stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...

ArsD and ArsR

ArsD is a trans-acting repressor of the arsRDABC operon that confers resistance to arsenicals and antimonials in ''Escherichia coli''. It possesses two-pairs of vicinal cysteine residues, Cys(12)-Cys(13) and Cys(112)-Cys(113), that potentially form separate

binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...

s for the metalloids that trigger

dissociation Dissociation, in the wide sense of the word, is an act of disuniting or separating a complex object into parts. Dissociation may also refer to: * Dissociation (chemistry), general process in which molecules or ionic compounds (complexes, or salts ...

of ArsD from the operon. However, as a

homodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

it has four vicinal cysteine

pairs Concentration, also known as Memory, Shinkei-suijaku (Japanese meaning "nervous breakdown"), Matching Pairs, Match Match, Match Up, Pelmanism, Pexeso or simply Pairs, is a card game in which all of the cards are laid face down on a surface and tw ...

. The ArsD family consists of several

l arsenical resistance

trans-acting In the field of molecular biology, ''trans''-acting (''trans''-regulatory, ''trans''-regulation), in general, means "acting from a different molecule" (''i.e.'', intermolecular). It may be considered the opposite of ''cis''-acting (''cis''-regula ...

repressor ArsD

s. ArsR is a trans-acting regulatory protein. It acts as a repressor on the arsRDABC operon when no arsenic is present in the cell. When arsenic is present in the cell ArsR will lose affinity for the operator and RNA polymerase can transcribe the arsDCAB genes. ArsD and ArsR work together to regulate the ars operon. arsenic chaperone, ArsD, encoded by the arsRDABC operon of Escherichia coli. ArsD transfers trivalent metalloids to ArsA, the catalytic subunit of an As(III)/Sb(III) efflux pump. Interaction with ArsD increases the affinity of ArsA for arsenite, thus increasing its ATPase activity at lower concentrations of arsenite and enhancing the rate of arsenite extrusion.

References

{{InterPro content, IPR010712 Protein families Operons