Selenocysteine

Selenocysteine

Names
IUPAC name 3-Selanyl-2-aminopropanoic acid
Other names L-Selenocysteine; 3-Selanyl-L-alanine; Selenium cysteine
Identifiers
CAS Number	10236-58-5 N
ChEBI	CHEBI:16633 Y
ChEMBL	ChEMBL109962 Y
ChemSpider	23436 Y
DrugBank	DB02345 Y
Jmol 3D model	Interactive image
KEGG	C05688 Y
PubChem	25076
UNII	0CH9049VIS N
InChI InChI=1S/C3H7NO2Se/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1 Y Key: ZKZBPNGNEQAJSX-REOHCLBHSA-N Y InChI=1/C3H7NO2Se/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1 Key: ZKZBPNGNEQAJSX-REOHCLBHBZ
SMILES O=C(O)[C@@H](N)C[SeH]
Properties
Chemical formula	C3H7NO2Se
Molar mass	168.07 g·mol−1
Vapor pressure	{{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Selenocysteine (abbreviated as Sec or U, in older publications also as Se-Cys) is the 21st proteinogenic amino acid.

Selenocysteine exists naturally in all kingdoms of life as a building block of selenoproteins. Selenocysteine is a cysteine analogue with a selenium-containing selenol group in place of the sulfur-containing thiol group.

Selenocysteine is present in several enzymes (for example glutathione peroxidases, tetraiodothyronine 5' deiodinases, thioredoxin reductases, formate dehydrogenases, glycine reductases, selenophosphate synthetase 2, methionine-R-sulfoxide reductase B1 (SEPX1), and some hydrogenases).

Selenocysteine was discovered by biochemist Thressa Stadtman at the National Institutes of Health.

Structure

Selenocysteine has a structure similar to that of cysteine, but with an atom of selenium taking the place of the usual sulfur, forming a selenol group which is deprotonated at physiological pH. Proteins that contain one or more selenocysteine residues are called selenoproteins and those with catalytic activities which depend on selenocysteine's biochemical activity are called selenoenzymes. The structurally characterized selenoenzymes have been found to employ catalytic triad structures that influence the nucleophilicity of the active site selenocysteine.

Biology

Selenocysteine has both a lower pKa (5.47) and a lower reduction potential than cysteine. These properties make it very suitable in proteins that are involved in antioxidant activity.

Although it is found in all kingdoms of life, it is not universal in all organisms. Unlike other amino acids present in biological proteins, selenocysteine is not coded for directly in the genetic code. Instead, it is encoded in a special way by a UGA codon, which is normally a stop codon. Such a mechanism is called translational recoding and its efficiency depends on the selenoprotein being synthesized and on translation initiation factors. 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. The SECIS element is defined by characteristic nucleotide sequences and secondary structure base-pairing patterns. In bacteria, the SECIS element is typically located immediately following the UGA codon within the reading frame for the selenoprotein. In Archaea and in eukaryotes, the SECIS element is in the 3' untranslated region (3' UTR) of the mRNA, and can direct multiple UGA codons to encode selenocysteine residues.

Again 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 selenide form (H₂Se). Selenocysteine synthesis occurs on a specialized tRNA, 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 (bacteria) or 10-base (eukaryotes) pair 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 in bacteria, eEF1A in eukaryotes).

Rather, the tRNA-bound seryl residue is converted to a selenocysteine residue by the pyridoxal phosphate-containing enzyme 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.

As of 2003, twenty-five human proteins are known to contain selenocysteine (selenoproteins).

Selenocysteine derivatives γ-glutamyl-Se-methylselenocysteine and Se-methylselenocysteine occur naturally in plants of the genera Allium and Brassica.

Applications

Biotechnological applications of selenocysteine include use of ⁷³Se-labeled Sec (half-life of ⁷³Se = 7.2 hours) in positron emission tomography (PET) studies and ⁷⁵Se-labeled Sec (half-life of ⁷⁵Se = 118.5 days) in specific radiolabeling, facilitation of phase determination by multi-wavelength anomalous diffraction in X-ray crystallography of proteins by introducing Sec alone, or Sec together with selenomethionine (SeMet), and incorporation of the stable ⁷⁷Se isotope, which has a nuclear spin of 1/2 and can be used for high-resolution NMR, among others.

See also

• Pyrrolysine, another amino acid not in the basic set of 20.
• Selenomethionine, another selenium-containing amino acid, which is randomly substituted for methionine.