# Threonine—tRNA ligase

Last updated
threonine-tRNA ligase
Identifiers
EC number 6.1.1.3
CAS number 9023-46-5
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures
Gene Ontology

In enzymology, a threonine-tRNA ligase (EC 6.1.1.3) is an enzyme that catalyzes the chemical reaction

The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme.

Catalysis is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst, which is not consumed in the catalyzed reaction and can continue to act repeatedly. Because of this, only very small amounts of catalyst are required to alter the reaction rate in principle.

A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking of chemical bonds between atoms, with no change to the nuclei, and can often be described by a chemical equation. Nuclear chemistry is a sub-discipline of chemistry that involves the chemical reactions of unstable and radioactive elements where both electronic and nuclear changes can occur.

## Contents

ATP + L-threonine + tRNA(Thr) ${\displaystyle \rightleftharpoons }$ AMP + diphosphate + L-threonyl-tRNA(Thr)

The three substrates of this enzyme are ATP, L-threonine, and threonine-specific transfer RNA [tRNA(Thr)], whereas its three products are AMP, diphosphate, and L-threonyl-tRNA(Thr).

Adenosine triphosphate (ATP) is a complex organic chemical that provides energy to drive many processes in living cells, e.g. muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP so that the human body recycles its own body weight equivalent in ATP each day. It is also a precursor to DNA and RNA, and is used as a coenzyme.

A transfer RNA is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length, that serves as the physical link between the mRNA and the amino acid sequence of proteins. tRNA does this by carrying an amino acid to the protein synthetic machinery of a cell (ribosome) as directed by a 3-nucleotide sequence (codon) in a messenger RNA (mRNA). As such, tRNAs are a necessary component of translation, the biological synthesis of new proteins in accordance with the genetic code.

Products are the species formed from chemical reactions. During a chemical reaction reactants are transformed into products after passing through a high energy transition state. This process results in the consumption of the reactants. It can be a spontaneous reaction or mediated by catalysts which lower the energy of the transition state, and by solvents which provide the chemical environment necessary for the reaction to take place. When represented in chemical equations products are by convention drawn on the right-hand side, even in the case of reversible reactions. The properties of products such as their energies help determine several characteristics of a chemical reaction such as whether the reaction is exergonic or endergonic. Additionally the properties of a product can make it easier to extract and purify following a chemical reaction, especially if the product has a different state of matter than the reactants. Reactants are molecular materials used to create chemical reactions. The atoms aren't created or destroyed. The materials are reactive and reactants are rearranging during a chemical reaction. Here is an example of reactants: CH4 + O2. A non-example is CO2 + H2O or "energy".

The systematic name of this enzyme class is L-threonine:tRNAThr ligase (AMP-forming). Other names in common use include threonyl-tRNA synthetase, threonyl-transfer ribonucleate synthetase, threonyl-transfer RNA synthetase, threonyl-transfer ribonucleic acid synthetase, threonyl ribonucleic synthetase, threonine-transfer ribonucleate synthetase, threonine translase, threonyl-tRNA synthetase, and TARS.

Threonine—tRNA ligase (TARS) belongs to the family of ligases, to be specific those forming carbon-oxygen bonds in tRNA and related compounds. More precisely, it belongs to the family of the aminoacyl-tRNA synthetases. These latter enzymes link amino acids to their cognate transfer RNAs (tRNA) in aminoacylation reactions that establish the connection between a specific amino acid and a nucleotide triplet anticodon embedded in the tRNA. During their long evolution, some of these enzymes have acquired additional functions, including roles in RNA splicing, RNA trafficking, transcriptional regulation, translational regulation, and cell signaling.

In biochemistry, a ligase is an enzyme that can catalyze the joining of two large molecules by forming a new chemical bond, usually with accompanying hydrolysis of a small pendant chemical group on one of the larger molecules or the enzyme catalyzing the linking together of two compounds, e.g., enzymes that catalyze joining of C-O, C-S, C-N, etc. In general, a ligase catalyzes the following reaction:

Amino acids are organic compounds that contain amine (-NH2) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. About 500 naturally occurring amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways. They can be classified according to the core structural functional groups' locations as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, pH level, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid residues form the second-largest component (water is the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis.

Nucleotides are organic molecules that serve as the monomer units for forming the nucleic acid polymers deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are the building blocks of nucleic acids; they are composed of three sub unit molecules: a nitrogenous base, a five-carbon sugar, and at least one phosphate group.

## Structural studies

As of late 2007, 17 structures have been solved for this class of enzymes, with PDB accession codes 1EVK, 1EVL, 1FYF, 1KOG, 1NYQ, 1NYR, 1QF6, 1TJE, 1TKE, 1TKG, 1TKY, 1WWT, 1Y2Q, 2HKZ, 2HL0, 2HL1, and 2HL2.

The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cryo-electron microscopy, and submitted by biologists and biochemists from around the world, are freely accessible on the Internet via the websites of its member organisations. The PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB.

## Translational regulation

Threonyl-tRNA synthetase (TARS) from Escherichia coli is encoded by the thrS gene. It is a homodimeric enzyme that aminoacylates tRNA(Thr) with the amino acid threonine. [1] In addition, TARS has the ability to bind to its own messenger RNA (mRNA) immediately upstream of the AUG start codon, to inhibit its translation by competing with ribosome binding, and thus to negatively regulate the expression of its own gene. The cis-acting region responsible for the control, called operator, can be folded into four distinct domains. [2] Each of domains 2 and 4 can be folded in a stem and loop structure that mimics the anticodon arm of E. coli tRNA(Thr). Mutagenesis and biochemical experiments have shown that the two anticodon-like domains of the operator bind to the two tRNA(Thr) anticodon recognition sites (one per subunit) of the dimeric TARS in a quasi-symmetrical manner. [3] [4]

In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

Threonine is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, a carboxyl group, and a side chain containing a hydroxyl group, making it a polar, uncharged amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Threonine is synthesized from aspartate in bacteria such as E. coli. It is encoded by all the codons starting AC.

Messenger RNA (mRNA) is a large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression. The RNA polymerase enzyme transcribes genes into primary transcript mRNA leading to processed, mature mRNA. This mature mRNA is then translated into a polymer of amino acids: a protein, as summarized in the central dogma of molecular biology.

The crystal structures of (i) TARS complexed with two tRNA(Thr) molecules, [5] and (ii) TARS complexed with two isolated domains 2, [6] have confirmed that TARS recognition is primarily governed by similar base-specific interactions between the anticodon loop of tRNA(Thr) and the loop of the operator domain 2. The same amino acids interact with the CGU anticodon sequence of tRNA(Thr) and the analogous residues in domain 2.

## Related Research Articles

An aminoacyl-tRNA synthetase, also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its tRNA. It does so by catalyzing the esterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code.

In enzymology, an alanine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, an arginine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, an aspartate-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a glutamate-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a glutamine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, an isoleucine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a leucine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a lysine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a methionine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a phenylalanine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a phosphopantothenate-cysteine ligase also known as phosphopantothenoylcysteine synthetase (PPCS) is an enzyme that catalyzes the chemical reaction which constitutes the second of five steps involved in the conversion of pantothenate to Coenzyme A. The reaction is:

In molecular biology, the protein domain SAICAR synthase is an enzyme which catalyses a reaction to create SAICAR. In enzymology, this enzyme is also known as phosphoribosylaminoimidazolesuccinocarboxamide synthase. It is an enzyme that catalyzes the chemical reaction

In enzymology, a proline—tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a serine-tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a tryptophan-tRNA ligase is an enzyme that catalyzes the chemical reaction

Tyrosine—tRNA ligase, also known as tyrosyl-tRNA synthetase, is an enzyme that catalyzes the chemical reaction

In enzymology, a valine-tRNA ligase is an enzyme that catalyzes the chemical reaction

Threonyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the TARS gene.

TRNAIle-lysidine synthase (EC 6.3.4.19, TilS, mesJ (gene), yacA (gene), isoleucine-specific transfer ribonucleate lysidine synthetase, tRNAIle-lysidine synthetase) is an enzyme with systematic name L-lysine:(tRNAIle2)-cytidine34 ligase (AMP-forming). This enzyme catalyses the following chemical reaction

## References

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2. Brunel, C; Caillet, J; Lesage, P; Graffe, M; Dondon, J; Moine, H; Romby, P; Ehresmann, C; Ehresmann, B; Grunberg-Manago, M; Springer, M (Oct 1992). "Domains of the Escherichia coli threonyl-tRNA synthetase translational operator and their relation to threonine tRNA isoacceptors". J Mol Biol. 227 (3): 621–634. doi:10.1016/0022-2836(92)90212-3. PMID   1383551.
3. Bedouelle, Hugues (Apr 1993). "Symmetrical interactions between the translational operator of the thrS gene and dimeric threonyl transfer RNA synthetase". J Mol Biol. 230 (3): 704–708. doi:10.1006/jmbi.1993.1190. PMID   7683056.
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5. Sankaranarayanan, R; Dock-Bregeon, AC; Romby, P; Caillet, J; Springer, M; Rees, B; Ehresmann, C; Ehresmann, B; Moras, D (Apr 1999). "The structure of threonyl-tRNA synthetase-tRNA(Thr) complex enlightens its repressor activity and reveals an essential zinc ion in the active site". Cell. 97 (3): 371–381. doi:10.1016/s0092-8674(00)80746-1. PMID   10319817.
6. Torres-Larios, A; Dock-Bregeon, AC; Romby, P; Rees, B; Sankaranarayanan, R; Caillet, J; Springer, M; Ehresmann, C; Ehresmann, B; Moras, D (May 2002). "Structural basis of translational control by Escherichia coli threonyl tRNA synthetase". Nat Struct Biol. 9 (5): 343–347. doi:10.1038/nsb789. PMID   11953757.
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