2',3'-Cyclic-nucleotide 3'-phosphodiesterase
Encyclopedia
2',3'-Cyclic-nucleotide 3'-phosphodiesterase also known as CNPase is an enzyme
that in humans is encoded by the CNP gene
.
Thus, the two substrates
of this enzyme are nucleoside 2',3'-cyclic phosphate and H2O
, whereas its product
is nucleoside 2'-phosphate.
-associated enzyme that makes up 4% of total CNS
myelin protein, and is thought to undergo significant age-associated changes. It is named for its ability to catalyze the phosphodiester
hydrolysis
of 2',3'-cyclic nucleotides to 2'-nucleotides, though a cohesive understanding of its specific physiologic functions are still ambiguous.
Structural studies have revealed that four classes of CNPs belong to one protein superfamily. CNP's catalytic core consists of three alpha-helices
and nine beta-strands
. The proposed mechanism of CNPs phosphodiesterase
catalytic activity is similar to the second step of the reaction mechanism for RNase A
.
CNP is expressed exclusively by oligodendrocyte
s in the CNS, and the appearance of CNP seems to be one of the earliest events of oligodendrocyte differentiation. CNP is thought to play a critical role in the events leading up to myelination.
CNP also associates with microtubule
s in brain tissue and FRTL-5 thyroid cells, and is reported to have microtubule-associated protein
-like activity (MAP; see MAP2
), being able to catalyze microtubule formation at low molar ratios. Deletion of the C-terminus of CNP or phosphorylation
abolish the catalytic activity of microtubule formation. CNP can link tubulin to cellular membranes, and might be involved in the regulation cytoplasmic microtubule distribution.
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 in humans is encoded by the CNP gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Reaction
CNPase catalyzes the following reaction:- nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
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 nucleoside 2',3'-cyclic phosphate and H2O
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
, whereas its product
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...
is nucleoside 2'-phosphate.
Function
CNPase is a myelinMyelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
-associated enzyme that makes up 4% of total CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
myelin protein, and is thought to undergo significant age-associated changes. It is named for its ability to catalyze the phosphodiester
Phosphodiester bond
A phosphodiester bond is a group of strong covalent bonds between a phosphate group and two 5-carbon ring carbohydrates over two ester bonds. Phosphodiester bonds are central to all known life, as they make up the backbone of each helical strand of DNA...
hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
of 2',3'-cyclic nucleotides to 2'-nucleotides, though a cohesive understanding of its specific physiologic functions are still ambiguous.
Structural studies have revealed that four classes of CNPs belong to one protein superfamily. CNP's catalytic core consists of three alpha-helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
and nine beta-strands
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
. The proposed mechanism of CNPs phosphodiesterase
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
catalytic activity is similar to the second step of the reaction mechanism for RNase A
Ribonuclease A
Ribonuclease A is a pancreatic ribonuclease that cleaves single-stranded RNA. Bovine pancreatic RNase A is one of the classic model systems of protein science.-History:...
.
CNP is expressed exclusively by oligodendrocyte
Oligodendrocyte
Oligodendrocytes , or oligodendroglia , are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons in the central nervous system of some vertebrates...
s in the CNS, and the appearance of CNP seems to be one of the earliest events of oligodendrocyte differentiation. CNP is thought to play a critical role in the events leading up to myelination.
CNP also associates with microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
s in brain tissue and FRTL-5 thyroid cells, and is reported to have microtubule-associated protein
Microtubule-associated protein
In cell biology, microtubule-associated proteins are proteins that interact with the microtubules of the cellular cytoskeleton.-Function:...
-like activity (MAP; see MAP2
MAP2
Microtubule-associated protein 2 is a protein that in humans is encoded by the MAP2 gene.-Interactions:MAP2 has been shown to interact with Grb2, NEFL and MYO7A.. MAP2 is suspected of interacting with tubulin.-Further reading:...
), being able to catalyze microtubule formation at low molar ratios. Deletion of the C-terminus of CNP or phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
abolish the catalytic activity of microtubule formation. CNP can link tubulin to cellular membranes, and might be involved in the regulation cytoplasmic microtubule distribution.