Selenocysteine (symbol Sec or U, in older publications also as Se-Cys) is the 21st
proteinogenic amino acid
Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino aci ...
.
Selenoproteins In molecular biology a selenoprotein is any protein that includes a selenocysteine (Sec, U, Se-Cys) amino acid residue. Among functionally characterized selenoproteins are five glutathione peroxidases (GPX) and three thioredoxin reductases, (TrxR/TX ...
contain selenocysteine residues. Selenocysteine is an analogue of the more common
cysteine with
selenium
Selenium is a chemical element with the symbol Se and atomic number 34. It is a nonmetal (more rarely considered a metalloid) with properties that are intermediate between the elements above and below in the periodic table, sulfur and tellurium, ...
in place of the
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
.
Selenocysteine is present in several
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 ...
s (for example
glutathione peroxidase
Glutathione peroxidase (GPx) () is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid h ...
s,
tetraiodothyronine 5′ deiodinases,
thioredoxin reductase
Thioredoxin reductases (TR, TrxR) () are enzymes that reduce thioredoxin (Trx). Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. In bacteria TrxR also catalyzes the reduction ...
s,
formate dehydrogenase
Formate dehydrogenases are a set of enzymes that catalyse the oxidation of formate to carbon dioxide, donating the electrons to a second substrate, such as NAD+ in formate:NAD+ oxidoreductase () or to a cytochrome in formate:ferricytochrome-b1 o ...
s,
glycine reductases,
selenophosphate synthetase 2, methionine-''R''-sulfoxide reductase B1 (
SEPX1
Methionine-R-sulfoxide reductase B1 is an enzyme that in humans is encoded by the ''SEPX1'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''gene ...
), and some
hydrogenase A hydrogenase is an enzyme that catalyses the reversible oxidation of molecular hydrogen (H2), as shown below:
Hydrogen uptake () is coupled to the reduction of electron acceptors such as oxygen, nitrate, sulfate, carbon dioxide (), and fumarat ...
s). It occurs in all three
domains of life, including important enzymes (listed above) present in humans.
Selenocysteine was discovered by biochemist
Thressa Stadtman
Thressa Campbell Stadtman (February 12, 1920 – December 11, 2016) was an American biochemist, notable for her discovery of selenocysteine, and her research on selenoproteins and bioenergetics. In addition she made significant advances in amino a ...
at the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
.
Chemistry
Selenocysteine is the Se-analogue of cysteine. It is rarely encountered outside of living tissue (and is not available commercially) because it is very susceptible to air-oxidation. More common is the oxidized derivative selenocystine, which has an Se-Se bond. Both selenocysteine and selenocystine are white solids. The Se-H group is more acidic (
p''K''a = 5.43) than the thiol group; thus, it is
deprotonated
Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.ed ...
at physiological
pH.
Structure
Selenocysteine has the same structure as
cysteine, but with an atom of
selenium
Selenium is a chemical element with the symbol Se and atomic number 34. It is a nonmetal (more rarely considered a metalloid) with properties that are intermediate between the elements above and below in the periodic table, sulfur and tellurium, ...
taking the place of the usual sulfur. It has a
selenol
Selenols are organic compounds that contain the functional group with the connectivity C– Se–H. Selenols are sometimes also called selenomercaptans and selenothiols. Selenols are one of the principal classes of organoselenium compounds. The be ...
group. Like other natural proteinogenic amino acids, cysteine and selenocysteine have
chirality
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from ...
in the older / notation based on homology to - and -
glyceraldehyde
Glyceraldehyde (glyceral) is a triose monosaccharide with chemical formula C3 H6 O3. It is the simplest of all common aldoses. It is a sweet, colorless, crystalline solid that is an intermediate compound in carbohydrate metabolism. The word comes ...
. In the newer ''R''/''S'' system of designating chirality, based on the atomic numbers of atoms near the asymmetric carbon, they have ''R'' chirality, because of the presence of sulfur or selenium as a second neighbor to the asymmetric carbon. The remaining chiral amino acids, having only lighter atoms in that position, have ''S'' chirality.)
Proteins which contain a selenocysteine residue are called
selenoprotein In molecular biology a selenoprotein is any protein that includes a selenocysteine (Sec, U, Se-Cys) amino acid residue. Among functionally characterized selenoproteins are five glutathione peroxidases (GPX) and three thioredoxin reductases, (TrxR/TX ...
s. Most selenoproteins contain a single selenocysteine residue. Selenoproteins that exhibit catalytic activity are called selenoenzymes.
Biology
Selenocysteine has a lower
reduction potential
Redox potential (also known as oxidation / reduction potential, ''ORP'', ''pe'', ''E_'', or E_) is a measure of the tendency of a chemical species to acquire electrons from or lose electrons to an electrode and thereby be reduced or oxidised respe ...
than cysteine. These properties make it very suitable in proteins that are involved in
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
activity.
Although it is found in the
three domains of life, it is not universal in all organisms. Unlike other amino acids present in biological
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s, selenocysteine is not coded for directly in the
genetic code
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
. Instead, it is encoded in a special way by a UGA
codon, which is normally the "opal"
stop codon
In molecular biology (specifically protein biosynthesis), a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in me ...
. Such a mechanism is called translational
recoding and its efficiency depends on the selenoprotein being synthesized and on translation
initiation factor Initiation factors are proteins that bind to the small subunit of the ribosome during the initiation of translation, a part of protein biosynthesis.
Initiation factors can interact with repressors to slow down or prevent translation. They have t ...
s. When cells are grown in the absence of selenium, translation of selenoproteins terminates at the UGA codon, resulting in a truncated, nonfunctional enzyme. The UGA codon is made to encode selenocysteine by the presence of a
selenocysteine insertion sequence (SECIS) in the
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
. The SECIS element is defined by characteristic nucleotide sequences and secondary structure base-pairing patterns. In
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, the SECIS element is typically located immediately following the UGA codon within the reading frame for the selenoprotein. In
Archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
and in
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s, the SECIS element is in the
3′ untranslated region (3′ UTR) of the mRNA and can direct multiple UGA codons to encode selenocysteine residues.
Unlike the other amino acids, no free pool of selenocysteine exists in the cell. Its high reactivity would cause damage to cells. Instead, cells store selenium in the less reactive oxidized form, selenocystine, or in methylated form, selenomethionine. Selenocysteine synthesis occurs on a specialized
tRNA
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
, which also functions to incorporate it into nascent polypeptides.
The primary and secondary structure of selenocysteine-specific tRNA, tRNA
Sec, differ from those of standard tRNAs in several respects, most notably in having an 8-base-pair (bacteria) or 10-base-pair (eukaryotes) acceptor stem, a long variable region arm, and substitutions at several well-conserved base positions. The selenocysteine tRNAs are initially charged with serine by
seryl-tRNA ligase, but the resulting Ser-tRNA
Sec is not used for translation because it is not recognised by the normal translation elongation factor (
EF-Tu
EF-Tu (elongation factor thermo unstable) is a prokaryotic elongation factor responsible for catalyzing the binding of an aminoacyl-tRNA (aa-tRNA) to the ribosome. It is a G-protein, and facilitates the selection and binding of an aa-tRNA to t ...
in bacteria,
eEF1A in eukaryotes).
Rather, the tRNA-bound seryl residue is converted to a selenocysteine residue by the
pyridoxal phosphate
Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent a ...
-containing enzyme
selenocysteine synthase. In eukaryotes and archaea, two enzymes are required to convert tRNA-bound seryl residue into tRNA selenocysteinyl residue: PSTK (''O''-phosphoseryl-tRNA
erec kinase) and selenocysteine synthase. Finally, the resulting Sec-tRNA
Sec is specifically bound to an alternative translational elongation factor (SelB or mSelB (or eEFSec)), which delivers it in a targeted manner to the ribosomes translating mRNAs for selenoproteins. The specificity of this delivery mechanism is brought about by the presence of an extra protein domain (in bacteria, SelB) or an extra subunit (
SBP2 for eukaryotic mSelB/eEFSec) which bind to the corresponding RNA secondary structures formed by the SECIS elements in selenoprotein mRNAs.
Selenocysteine is decomposed by the enzyme
selenocysteine lyase into
L-
alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side ...
and selenide.
, 136 human proteins (in 37 families) are known to contain selenocysteine (selenoproteins).
Selenocysteine derivatives γ-glutamyl-''Se''-methylselenocysteine and
''Se''-methylselenocysteine occur naturally in plants of the genera ''
Allium
''Allium'' is a genus of monocotyledonous flowering plants that includes hundreds of species, including the cultivated onion, garlic, scallion, shallot, leek, and chives. The generic name ''Allium'' is the Latin word for garlic,Gledhill, Davi ...
'' and ''
Brassica
''Brassica'' () is a genus of plants in the cabbage and mustard family (Brassicaceae). The members of the genus are informally known as cruciferous vegetables, cabbages, or mustard plants. Crops from this genus are sometimes called ''cole cr ...
''.
Applications
Biotechnological applications of selenocysteine include use of
73Se-labeled Sec (half-life of
73Se = 7.2 hours) in
positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
(PET) studies and
75Se-labeled Sec (half-life of
75Se = 118.5 days) in specific
radiolabel
A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...
ing, facilitation of phase determination by
multiwavelength anomalous diffraction in
X-ray crystallography
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
of proteins by introducing Sec alone, or Sec together with
selenomethionine
Selenomethionine (SeMet) is a naturally occurring amino acid. The L-selenomethionine enantiomer is the main form of selenium found in Brazil nuts, cereal grains, soybeans, and grassland legumes, while ''Se''-methylselenocysteine, or its γ-gluta ...
(SeMet), and incorporation of the stable
77Se isotope, which has a
nuclear spin of and can be used for high-resolution
NMR
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...
, among others.
See also
*
Pyrrolysine
Pyrrolysine (symbol Pyl or O; encoded by the 'amber' stop codon UAG) is an α-amino acid that is used in the biosynthesis of proteins in some methanogenic archaea and bacteria; it is not present in humans. It contains an α-amino group (which is ...
, another amino acid not in the basic set of 20.
*
Selenomethionine
Selenomethionine (SeMet) is a naturally occurring amino acid. The L-selenomethionine enantiomer is the main form of selenium found in Brazil nuts, cereal grains, soybeans, and grassland legumes, while ''Se''-methylselenocysteine, or its γ-gluta ...
, another selenium-containing amino acid, which is randomly substituted for methionine.
References
Further reading
*
*
*
*
External links
For the first time a Uruguayan scientist finds selenocysteine in fungi
{{selenium compounds
Amino acids
Proteinogenic amino acids
Selenols
Amino alcohols