molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

, an arginine finger is an amino acid residue of some

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. A ...

s. Arginine fingers are often found in the

protein superfamily A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology (biology), homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if n ...

AAA+ AAA, Triple A, or Triple-A is a three-letter initialism or abbreviation which may refer to: Airports * Anaa Airport in French Polynesia (IATA airport code AAA) * Logan County Airport (Illinois) (FAA airport code AAA) Arts, entertainment, and me ...

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...

GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a pro ...

s, and

dUTPase In Enzymology, a dUTP diphosphatase () is an enzyme that catalysis, catalyzes the chemical reaction :dUTP + H2O \rightleftharpoons dUMP + diphosphate Thus, the two substrate (biochemistry), substrates of this enzyme are Deoxyuridine triphosph ...

s, where they assist in the catalysis of the gamma

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

or gamma and beta phosphates from ATP or GTP, which creates a release of energy which can be used to perform cellular

work Work may refer to: * Work (human activity), intentional activity people perform to support themselves, others, or the community ** Manual labour, physical work done by humans ** House work, housework, or homemaking ** Working animal, an animal tr ...

. Thus, they are essential for many forms of life, and are highly conserved. Arginine fingers function through

non-covalent interaction In chemistry, a non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The c ...

s. They may also assist in dimerization, and while they are found in a wide variety of enzymes, they are not ubiquitous.

Role in catalytic mechanisms

Generally, the role of the arginine finger in catalysis is to function in

transition state In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked wi ...

stabilization to allow water to perform a

nucleophilic attack In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

to cleave off a number of phosphate groups. However, there are exceptions, and arginine fingers can assist in other roles. Additionally, arginine fingers may be attached to different subunits or other proteins in a

multiprotein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein c ...

. Arginine fingers sometimes interact with

guanidinium Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experien ...

during their role in catalysis.

dUTPases

Arginine fingers often work with other features in their assistance of catalysis. For example, in some trimeric

s, such as those of ''M. tuberculosis'', arginine fingers at the 64th and 140th residue can work with

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...

to cleave dUTP into dUMP and a

pyrophosphate In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P–O–P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among other ...

. The underlying mechanism of action for this is a nucleophilic attack; the positively charged magnesium ion () pulls on an oxygen of the beta and gamma phosphates to allow water to

hydrolyze Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

the bond between the beta and alpha phosphates. The arginine fingers help stabilize the transition state. Arginine fingers often interact with other motifs such as the

Walker motifs The Walker A and Walker B motifs are protein sequence motifs, known to have highly conserved three-dimensional structures. These were first reported in ATP-binding proteins by Walker and co-workers in 1982. Of the two motifs, the A motif is ...

and to perform catalysis more efficiently.

Ras GTPases

Arginine fingers are also present in

Ras GTPase Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals ...

s, where they help cleave GTP to turn Ras off. Ras is a

which functions in

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

to regulate

cell growth Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...

and

division Division or divider may refer to: Mathematics *Division (mathematics), the inverse of multiplication *Division algorithm, a method for computing the result of mathematical division Military *Division (military), a formation typically consisting ...

. In addition to being positively charged, which helps arginine fingers function as a catalyst, the arginine finger in Ras displaces solvent molecules and creates an optional charge distribution. Like those of dUPTases, the arginine fingers of Ras GTPases are assisted by a magnesium ion. Furthermore, multiple arginine finger residues can all point towards the same point, thus focusing their effect. Mutations affecting the arginine fingers of Ras lead to trouble catalyzing GTP by factors of around two to five

orders of magnitude An order of magnitude is an approximation of the logarithm of a value relative to some contextually understood reference value, usually 10, interpreted as the base of the logarithm and the representative of values of magnitude one. Logarithmic dis ...

. Thus, as Ras is an

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

and is activated and deactivated by the hydrolysis of GTP, mutations in Ras's arginine finger residues can lead to cancer.

Glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

also plays a role near arginine fingers and is stabilized by the arginines'

backbone chain In polymer science, the polymer chain or simply backbone of a polymer is the main chain of a polymer. Polymers are often classified according to the elements in the main chains. The character of the backbone, i.e. its flexibility, determines the ...

carboxyl groups, which are known as knuckles.

Heterotrimeric G proteins

heterotrimeric G protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest no ...

s, catalysis of GTP can be assisted by aluminum tetrafluoride () and

RGS4 Regulator of G protein signaling 4 also known as RGP4 is a protein that in humans is encoded by the ''RGS4'' gene. RGP4 regulates G protein signaling. Function Regulator of G protein signalling (RGS) family members are regulatory molecules that ...

. Heterotrimeric G proteins are larger three-part proteins serve in signal transduction of many pathways. The catalytic mechanism for GTP hydrolysis in heterotrimeric G proteins consists of an active state where catalysis is likely to occur and an inactive state where catalysis is unlikely. In the active state, stabilizes the transition state and points the arginine finger residue towards GTP. This causes increased

charge density In electromagnetism, charge density is the amount of electric charge per unit length, surface area, or volume. Volume charge density (symbolized by the Greek letter ρ) is the quantity of charge per unit volume, measured in the SI system in co ...

on the beta phosphate of GTP and

planarization In the mathematical field of graph theory, planarization is a method of extending graph drawing methods from planar graphs to graphs that are not planar, by embedding the non-planar graphs within a larger planar graph... Planarization may be perf ...

of the gamma phosphate, which creates an opening and reduces

steric hindrance Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

for water to hydrolyze the

phosphoanhydride High-energy phosphate can mean one of two things: * The phosphate-phosphate (phosphoanhydride/phosphoric anhydride/macroergic/phosphagen) bonds formed when compounds such as adenosine diphosphate (ADP) and adenosine triphosphate (ATP) are created. ...

beta-gamma bond. This is because the gamma phosphate's bond to the beta phosphate bends, exposing its connection and allowing the subsequent

nucleophilic substitution In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...

reaction initiated by water. The complex formed with RGS4 assists in this process by creating strain on the bond between the gamma and beta phosphates and assisting in distributing more charge onto the beta phosphate.

ATP synthase

ATP synthase ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation ...

consists of a F₁ and F₀ subunit. The F₁ subunit contains alpha and beta subunits of its own which can assist in the formation of ATP, or hydrolyze it to serve as a

proton pump A proton pump is an integral membrane protein pump that builds up a proton gradient across a biological membrane. Proton pumps catalyze the following reaction: : n one side of a biological membrane/sub> + energy n the other side of the membr ...

. Though most catalytic actions happen on the beta subunits, the alpha subunits each contain an arginine finger. The role of the arginine finger in ATP synthase is akin to the function of the arginine finger residues of G proteins; to help split ATP. For example, if the arginine of the arginine finger is substituted by

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

, possibly due to a

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense m ...

, the αR364K mutant results. In the αR364K mutant, the ability of ATP synthase to hydrolyze ATP is decreased around a thousandfold compared to the

wild type The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "m ...

RecQ helicase

RecQ helicase RecQ helicase is a family of helicase enzymes initially found in ''Escherichia coli'' that has been shown to be important in genome maintenance. They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwind ...

is one of a family of

helicases Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separati ...

that helps reduce

sister chromatid exchange Sister chromatid exchange (SCE) is the exchange of genetic material between two identical sister chromatids. It was first discovered by using the Giemsa staining method on one chromatid belonging to the sister chromatid complex before anaphase in ...

during meiosis to lower mutation rates. RecQ helicases are found in many organisms, ranging from ''

E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'' to humans. One of these helicases, the

Bloom syndrome protein Bloom syndrome protein is a protein that in humans is encoded by the ''BLM'' gene and is not expressed in Bloom syndrome. The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimula ...

, contains an arginine finger which assists in its hydrolysis of ATP. In humans, the arginine finger of the Bloom syndrome protein is Arg982. The RecQ helicase, along with most proteins containing arginine fingers, is inhibited by

sodium orthovanadate Sodium orthovanadate is the inorganic compound with the chemical formula . It forms a dihydrate . Sodium orthovanadate is a salt of the oxyanion. It is a colorless, water-soluble solid. Synthesis and structure Sodium orthovanadate is produced by ...

, which interferes with the arginine finger residue.

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