Flavoprotein
Encyclopedia
Flavoproteins are proteins that contain a nucleic acid
derivative of riboflavin
: the flavin adenine dinucleotide (FAD) or flavin mononucleotide
(FMN).
Flavoproteins are involved in a wide array of biological processes, including, but by no means limited to, bioluminescence
, removal of radicals
contributing to oxidative stress, photosynthesis
, DNA repair
, and apoptosis
. The spectroscopic properties of the flavin cofactor make it a natural reporter for changes occurring within the active site
; this makes flavoproteins one of the most-studied enzyme families.
, that we now know as flavin, but termed lactochrome at the time. By the early 1930s, this same pigment had been isolated from a range of sources, and recognised as a component of the vitamin B complex. Its structure was determined almost simultaneously by two groups in 1934, and given the name riboflavin
, derived from the ribityl side chain and yellow colour of the conjugated ring system.
The first evidence for the requirement of flavin as an enzyme
cofactor
came in 1935. Hugo Theorell
and coworkers showed that a bright-yellow-coloured yeast
protein
, identified previously as essential for cellular respiration
, could be separated into apoprotein and a bright-yellow pigment. Neither apoprotein nor pigment alone could catalyse the oxidation of NADH, but mixing of the two restored the enzyme
activity. However, replacing the isolated pigment with riboflavin
did not restore enzyme activity, despite their being indistinguishable under spectroscopy
. This led to the discovery that the protein studied required not riboflavin but flavin mononucleotide
to be catalytically active
Similar experiments with D-amino acid oxidase
led to the identification of flavin adenine dinucleotide (FAD) as a second form of flavin utilised by enzymes.
External links
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
derivative of riboflavin
Riboflavin
Riboflavin, also known as vitamin B2 or additive E101, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a...
: the flavin adenine dinucleotide (FAD) or flavin mononucleotide
Flavin mononucleotide
Flavin mononucleotide , or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin by the enzyme riboflavin kinase and functions as prosthetic group of various oxidoreductases including NADH dehydrogenase as well as cofactor in biological blue-light photo receptors...
(FMN).
Flavoproteins are involved in a wide array of biological processes, including, but by no means limited to, bioluminescence
Bioluminescence
Bioluminescence is the production and emission of light by a living organism. Its name is a hybrid word, originating from the Greek bios for "living" and the Latin lumen "light". Bioluminescence is a naturally occurring form of chemiluminescence where energy is released by a chemical reaction in...
, removal of radicals
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
contributing to oxidative stress, photosynthesis
Photosynthesis
Photosynthesis is a chemical process that converts carbon dioxide into organic compounds, especially sugars, using the energy from sunlight. Photosynthesis occurs in plants, algae, and many species of bacteria, but not in archaea. Photosynthetic organisms are called photoautotrophs, since they can...
, DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
, and apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. The spectroscopic properties of the flavin cofactor make it a natural reporter for changes occurring within 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...
; this makes flavoproteins one of the most-studied enzyme families.
Discovery
The first mention of a flavoprotein in the scientific literature dates back to 1879, when the work on the composition of cow’s milk resulted in the isolation of a bright-yellow pigmentPigment
A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...
, that we now know as flavin, but termed lactochrome at the time. By the early 1930s, this same pigment had been isolated from a range of sources, and recognised as a component of the vitamin B complex. Its structure was determined almost simultaneously by two groups in 1934, and given the name riboflavin
Riboflavin
Riboflavin, also known as vitamin B2 or additive E101, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a...
, derived from the ribityl side chain and yellow colour of the conjugated ring system.
The first evidence for the requirement of flavin as an enzyme
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...
cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
came in 1935. Hugo Theorell
Hugo Theorell
Axel Hugo Theodor Theorell was a Swedish scientist and Nobel Prize laureate in medicine.He was born in Linköping as the son of Thure Theorell and his wife Armida Bill. Theorell went to Secondary School at Katedralskolan in Linköping and passed his examination there on 23 May 1921...
and coworkers showed that a bright-yellow-coloured 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...
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...
, identified previously as essential for cellular respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...
, could be separated into apoprotein and a bright-yellow pigment. Neither apoprotein nor pigment alone could catalyse the oxidation of NADH, but mixing of the two restored the enzyme
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...
activity. However, replacing the isolated pigment with riboflavin
Riboflavin
Riboflavin, also known as vitamin B2 or additive E101, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a...
did not restore enzyme activity, despite their being indistinguishable under spectroscopy
Spectroscopy
Spectroscopy is the study of the interaction between matter and radiated energy. Historically, spectroscopy originated through the study of visible light dispersed according to its wavelength, e.g., by a prism. Later the concept was expanded greatly to comprise any interaction with radiative...
. This led to the discovery that the protein studied required not riboflavin but flavin mononucleotide
Flavin mononucleotide
Flavin mononucleotide , or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin by the enzyme riboflavin kinase and functions as prosthetic group of various oxidoreductases including NADH dehydrogenase as well as cofactor in biological blue-light photo receptors...
to be catalytically active
Similar experiments with D-amino acid oxidase
D-amino acid oxidase
D-amino acid oxidase is a peroxisomal enzyme containing FAD as cofactor that is expressed in a wide range of species from yeasts to human. It is not present in bacteria or in plants...
led to the identification of flavin adenine dinucleotide (FAD) as a second form of flavin utilised by enzymes.
Examples
The flavoprotein family contains a diverse range of enzymes, including:- Epidermin biosynthesisBiosynthesisBiosynthesis 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...
protein, EpiD, which has been shown to be a flavoprotein that bindCompetitive inhibitionCompetitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the active site on the enzyme prevents binding of the substrate and vice versa.-Mechanism:...
s FMN. This 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...
catalysesCatalysisCatalysis 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 removal of two reducing equivalents from the cysteineCysteineCysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residueResidue (chemistry)In chemistry, residue is the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction....
of the C-terminal meso-lanthionineLanthionineLanthionine is a nonproteinogenic amino acid with the chemical formula . As the monosulfide analog of cystine, lanthionine is composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage...
of epidermin to form a --CC-- double bond.
- The B chain of dipicolinate synthaseSynthaseIn biochemistry, a synthase is an enzyme that catalyses a synthesis process.Following the EC number classification, they belong to the group of ligases, with lyases catalysing the reverse reaction....
, an enzyme which catalysesCatalysisCatalysis 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 formation of dipicolinic acidDipicolinic acidDipicolinic acid is a chemical compound which composes 5% to 15% of the dry weight of bacterial spores...
from dihydroxydipicolinic acid.
- Phenylacrylic acid decarboxylase , and enzyme which confers resistance to cinnamic acidCinnamic acidCinnamic acid is a white crystalline organic acid, which is slightly soluble in water.It is obtained from oil of cinnamon, or from balsams such as storax. It is also found in shea butter and is the best indication of its environmental history and post-extraction conditions...
in yeastYeastYeasts 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...
External links
- The menu "science" of the program STRAP provides A comprehensive collection of all flavo-proteins with known 3D-structure. It compares the protein structures to elucidate phylogenetic relationships.