Multicopper oxidase
Encyclopedia
In molecular biology, multicopper oxidases are enzymes which oxidise their substrate by accepting electron
s at a mononuclear copper centre
and transferring them to a trinuclear copper centre; dioxygen binds to the trinuclear centre and, following the transfer of four electrons, is reduced
to two molecule
s of water
. There are three spectroscopically different copper centres found in multicopper oxidases: type 1 (or blue), type 2 (or normal) and type 3 (or coupled binuclear). Multicopper oxidases consist of 2, 3 or 6 of these homologous
domains, which also share homology to the cupredoxins azurin and plastocyanin
. Structurally, these domains
consist of a cupredoxin-like fold, a beta-sandwich consisting of 7 strands in 2 beta-sheets, arranged in a Greek-key beta-barrel. Multicopper oxidases include:
In addition to the above enzymes there are a number of other protein
s that are similar to the multi-copper oxidases in terms of structure
and sequence, some of which have lost the ability to bind copper. These include: copper resistance protein A (copA) from a plasmid
in Pseudomonas syringae
; domain A of (non-copper binding) blood coagulation factors V (Fa V) and VIII (Fa VIII) ; yeast
FET3 required for ferrous
iron
uptake ; yeast
hypothetical protein YFL041w; and the fission yeast homologue
SpAC1F7.08.
Electron
The electron is a subatomic particle with a negative elementary electric charge. It has no known components or substructure; in other words, it is generally thought to be an elementary particle. An electron has a mass that is approximately 1/1836 that of the proton...
s at a mononuclear copper centre
Copper proteins
Copper proteins are proteins that contain one or more copper ions as prosthetic groups. The metal centres in the copper proteins can be classified into several types:...
and transferring them to a trinuclear copper centre; dioxygen binds to the trinuclear centre and, following the transfer of four electrons, is reduced
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
to two molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
s of water
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...
. There are three spectroscopically different copper centres found in multicopper oxidases: type 1 (or blue), type 2 (or normal) and type 3 (or coupled binuclear). Multicopper oxidases consist of 2, 3 or 6 of these homologous
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
domains, which also share homology to the cupredoxins azurin and plastocyanin
Plastocyanin
Plastocyanin is an important copper-containing protein involved in electron-transfer. The protein is monomeric, with a molecular weight around 10,500 Daltons, and 99 amino acids in most vascular plants...
. Structurally, these 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...
consist of a cupredoxin-like fold, a beta-sandwich consisting of 7 strands in 2 beta-sheets, arranged in a Greek-key beta-barrel. Multicopper oxidases include:
- CeruloplasminCeruloplasminCeruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...
(ferroxidase), a 6-domain enzymeEnzymeEnzymes 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...
found in the serumBlood serumIn blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
of mammalMammalMammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s and birdBirdBirds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s that oxidizes different inorganic and organic substances; exhibits internal sequence homology that appears to have evolvedEvolutionEvolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
from the triplication of a Cu-binding domain similar to that of laccase and ascorbate oxidase.
- LaccaseLaccaseLaccases are copper-containing oxidase enzymes that are found in many plants, fungi, and microorganisms. The copper is bound in several sites; Type 1, Type 2, and/or Type 3. The ensemble of types 2 and 3 copper is called a trinuclear cluster . Type 1 copper is available to action of solvents,...
(urishiol oxidase), a 3-domain enzyme found in fungiFungusA 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, which oxidizes different phenolsPhenolsIn organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of a hydroxyl group bonded directly to an aromatic hydrocarbon group...
and diamines. CueO is a laccase found in Escherichia coliEscherichia coliEscherichia 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...
that is involved in copper-resistance.
- Ascorbate oxidase , a 3-domain enzyme found in higher plants.
- Nitrite reductaseNitrite reductaseNitrite reductase refers to any of several classes of enzymes that catalyze the reduction of nitrite. There are two classes of NIR's. A multi haem enzyme reduces NO2 to a variety of products. Copper containing enzymes carry out a single electron transfer to produce nitric oxide.- Iron based...
, a 2-domain enzyme containing type-1 and type-2 copper centres.
In addition to the above enzymes there are a number of other protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that are similar to the multi-copper oxidases in terms of 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...
and sequence, some of which have lost the ability to bind copper. These include: copper resistance protein A (copA) from a plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
in Pseudomonas syringae
Pseudomonas syringae
Pseudomonas syringae is a rod shaped, Gram-negative bacterium with polar flagella. It is a plant pathogen which can infect a wide range of plant species, and exists as over 50 different pathovars, all of which are available to legitimate researches via international culture collections such as the...
; domain A of (non-copper binding) blood coagulation factors V (Fa V) and VIII (Fa VIII) ; yeast
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
FET3 required for ferrous
Ferrous
Ferrous , in chemistry, indicates a divalent iron compound , as opposed to ferric, which indicates a trivalent iron compound ....
iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
uptake ; yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
hypothetical protein YFL041w; and the fission yeast homologue
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
SpAC1F7.08.