enzymology 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 ...

, a nucleoside-phosphate kinase () is an

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 ...

that

catalyzes Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

the

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

:ATP + nucleoside phosphate

\rightleftharpoons

ADP + nucleoside diphosphate Thus, the two substrates of this enzyme are

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

and

nucleoside monophosphate Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules with ...

, whereas its two products are ADP and nucleoside diphosphate. This enzyme belongs to the family of

transferase A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of di ...

s, specifically those transferring phosphorus-containing groups (

phosphotransferase Phosphotransferases are a category of enzymes ( EC number 2.7) that catalyze phosphorylation reactions. The general form of the reactions they catalyze is: :A-P + B \rightleftharpoons B-P + A Where ''P'' is a phosphate group and A and B are the do ...

s) with a phosphate group as acceptor. The systematic name of this enzyme class is ATP:nucleoside-phosphate phosphotransferase. This enzyme is also called NMP-kinase, or nucleoside-monophosphate kinase.

Structure

A number of

crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystal, crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric pat ...

s have been solved for this class of enzymes, revealing that they share a common ATP

binding domain In molecular biology, binding domain is a protein domain which binds to a specific atom or molecule, such as calcium or DNA. A protein domain is a part of a protein sequence and a tertiary structure that can change or evolve, function, and live ...

. This section of the enzyme is commonly referred to as the P-loop, in reference to its interaction with the phosphoryl groups on

. This binding domain also consists of a

β 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 g ...

flanked by α helices. The -looptypically has the amino acid sequence of Gly-X-X-X-X-Gly-Lys. Similar sequences are found in many other nucleotide-binding proteins. Adenylate kinase 2

Mechanism

Metal ion interaction

To allow for interaction with this class of enzymes,

must first bind to a metal ion such as

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 ...

manganese Manganese is a chemical element with the symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese is a transition metal with a multifaceted array of industrial alloy use ...

. The metal ion forms a complex with the phosphoryl-group, as well as several water molecules. These water molecules then form

hydrogen bonds In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...

to a conserved

aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...

residue on the enzyme. The metal ion interaction facilitates binding by holding the

molecule in a position allowing for specific binding to the

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

and by providing additional points for binding between the substrate and the enzyme. This increases the

binding energy In physics and chemistry, binding energy is the smallest amount of energy required to remove a particle from a system of particles or to disassemble a system of particles into individual parts. In the former meaning the term is predominantly use ...

Conformational changes

Binding of

causes the P-loop to move, in turn making the lid domain lower and secure the

in place.

Nucleoside monophosphate Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules with ...

binding induces further changes that render the enzyme catalytically capable of facilitating a transfer of the phosphoryl group from

. The necessity of these

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or oth ...

s prevents the wasteful

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

. This enzyme mechanism is an example of

catalysis Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

by approximation: the nucleoside-phosphate kinase binds the substrates to bring them together in the correct position for the phosphoryl group to be transferred.

Biological function

Similar catalytic domains are present in a variety of proteins, including: *

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 ...

Myosin Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first myosin ...

, and other molecular

motor protein Motor proteins are a class of molecular motors that can move along the cytoplasm of cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump. Cellular functions ...

s * G protein and other proteins involved in signal transduction * Helicases for unwinding DNA and

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

Pyrimidine metabolism Pyrimidine biosynthesis occurs both in the body and through organic synthesis. ''De novo'' biosynthesis of pyrimidine ''De Novo'' biosynthesis of a pyrimidine is catalyzed by three gene products CAD, DHODH and UMPS. The first three enzymes of ...

Evolution

When a

phylogenetic tree A phylogenetic tree (also phylogeny or evolutionary tree Felsenstein J. (2004). ''Inferring Phylogenies'' Sinauer Associates: Sunderland, MA.) is a branching diagram or a tree showing the evolutionary relationships among various biological spec ...

composed of members of the nucleoside-phosphate kinase family was made, it showed that these enzymes had originally diverged from a common ancestor into long and short varieties. This first change was drastic – the three-dimensional structure of the lid domain changed significantly. Following the evolution of long and short varieties of NMP-kinases, smaller changes in the amino acid sequences resulted in the differentiation of subcellular localization.

References

{{Portal bar, Biology, border=no EC 2.7.4 Enzymes of known structure