ATP phosphoribosyltransferase
Encyclopedia
In enzymology, an ATP phosphoribosyltransferase is an enzyme
that catalyzes
the chemical reaction
Thus, the two substrates
of this enzyme are 1-(5-phospho-D-ribosyl)-ATP and diphosphate, whereas its two products
are ATP
and 5-phospho-alpha-D-ribose 1-diphosphate.
This enzyme belongs to the family of glycosyltransferase
s, specifically the pentosyltransferases. The systematic name of this enzyme class is 1-(5-phospho-D-ribosyl)-ATP:diphosphate phospho-alpha-D-ribosyl-transferase. Other names in common use include phosphoribosyl-ATP pyrophosphorylase, adenosine triphosphate phosphoribosyltransferase, phosphoribosyladenosine triphosphate:pyrophosphate, phosphoribosyltransferase, phosphoribosyl ATP synthetase, phosphoribosyl ATP:pyrophosphate phosphoribosyltransferase, phosphoribosyl-ATP:pyrophosphate-phosphoribosyl phosphotransferase, phosphoribosyladenosine triphosphate pyrophosphorylase, and phosphoribosyladenosine triphosphate synthetase.
This enzyme catalyses
the first step in the biosynthesis
of histidine
in bacteria
, fungi
and plants. It is a member of the larger phosphoribosyltransferase
superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases
in the presence of divalent
metal ion
s.
Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation
is based primarily on nutrient
conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular
conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP
, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP
and AMP
(which reflect the overall energy
status of the cell). As this pathway of histidine biosynthesis is present only in prokaryotes, plant
s and fungi, this enzyme is a promising target for the development of novel antimicrobial
compounds and herbicides.
ATP phosphoribosyltransferase is found in two distinct forms: a long form containing two catalytic domains
and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organism
s with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity.
The structure
s of the long form enzymes from Escherichia coli
and Mycobacterium tuberculosis
have been determined. The enzyme itself exists in equilibrium
between an active dimeric
form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates
and inhibitor
s of the enzyme. The two catalytic
domains are linked by a two-stranded beta-sheet and togther form a "periplasmic binding protein fold". A crevice between these domains contains the active site
. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitor
s such as histidine to the enzyme, thus regulating activity.
have been solved for this class of enzymes, with PDB
accession codes , , , , , , , , , and .
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that catalyzes
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
- 1-(5-phospho-D-ribosyl)-ATP + diphosphate
ATP + 5-phospho-alpha-D-ribose 1-diphosphate
Thus, the two substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
of this enzyme are 1-(5-phospho-D-ribosyl)-ATP and diphosphate, whereas its two products
Product (chemistry)
Product are formed during chemical reactions as reagents are consumed. Products have lower energy than the reagents and are produced during the reaction according to the second law of thermodynamics. The released energy comes from changes in chemical bonds between atoms in reagent molecules and...
are ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
and 5-phospho-alpha-D-ribose 1-diphosphate.
This enzyme belongs to the family of glycosyltransferase
Glycosyltransferase
Glycosyltransferases are enzymes that act as a catalyst for the transfer of a monosaccharide unit from an activated nucleotide sugar to a glycosyl acceptor molecule, usually an alcohol....
s, specifically the pentosyltransferases. The systematic name of this enzyme class is 1-(5-phospho-D-ribosyl)-ATP:diphosphate phospho-alpha-D-ribosyl-transferase. Other names in common use include phosphoribosyl-ATP pyrophosphorylase, adenosine triphosphate phosphoribosyltransferase, phosphoribosyladenosine triphosphate:pyrophosphate, phosphoribosyltransferase, phosphoribosyl ATP synthetase, phosphoribosyl ATP:pyrophosphate phosphoribosyltransferase, phosphoribosyl-ATP:pyrophosphate-phosphoribosyl phosphotransferase, phosphoribosyladenosine triphosphate pyrophosphorylase, and phosphoribosyladenosine triphosphate synthetase.
This enzyme catalyses
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the first step in the biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
in bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
and plants. It is a member of the larger phosphoribosyltransferase
Phosphoribosyltransferase
A phosphoribosyltransferase is a type of transferase enzyme.Types include:* Adenine phosphoribosyltransferase* Hypoxanthine-guanine phosphoribosyltransferase* Orotidine 5'-phosphate decarboxylase* Uracil phosphoribosyltransferase...
superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases
Nitrogenous base
A nitrogenous base is a nitrogen-containing molecule having the chemical properties of a base. It is an organic compound that owes its property as a base to the lone pair of electrons of a nitrogen atom. In biological sciences, nitrogenous bases are typically classified as the derivatives of two...
in the presence of divalent
Divalent
In chemistry, a divalent ion or molecule has a valence of two and thus can form two bonds with other ions or molecules. An older term for divalent is bivalent....
metal ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s.
Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation
Transcriptional regulation
Transcriptional regulation is the change in gene expression levels by altering transcription rates. -Regulation of transcription:Regulation of transcription controls when transcription occurs and how much RNA is created...
is based primarily on nutrient
Nutrient
A nutrient is a chemical that an organism needs to live and grow or a substance used in an organism's metabolism which must be taken in from its environment. They are used to build and repair tissues, regulate body processes and are converted to and used as energy...
conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
and AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...
(which reflect the overall energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...
status of the cell). As this pathway of histidine biosynthesis is present only in prokaryotes, plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s and fungi, this enzyme is a promising target for the development of novel antimicrobial
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
compounds and herbicides.
ATP phosphoribosyltransferase is found in two distinct forms: a long form containing two catalytic domains
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
s with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity.
The structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
s of the long form enzymes from Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
and Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
have been determined. The enzyme itself exists in equilibrium
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...
between an active dimeric
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
and inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
s of the enzyme. The two catalytic
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
domains are linked by a two-stranded beta-sheet and togther form a "periplasmic binding protein fold". A crevice between these domains contains the active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
s such as histidine to the enzyme, thus regulating activity.
Structural studies
As of late 2007, 10 structuresTertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
have been solved for this class of enzymes, with PDB
Protein Data Bank
The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
accession codes , , , , , , , , , and .