Selenocysteine[1]
|
| Names |
| IUPAC name
3-Selanyl-2-aminopropanoic acid
|
| Other names
L-Selenocysteine; 3-Selanyl-L-alanine; Selenium cysteine
|
| Identifiers |
|
CAS Number
|
|
|
3D model (JSmol)
|
|
| ChEBI |
|
| ChEMBL |
|
| ChemSpider |
|
| DrugBank |
|
| ECHA InfoCard |
100.236.386 |
| KEGG |
|
|
|
|
| UNII |
|
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
|
|
|
| Properties |
|
Chemical formula
|
C3H7NO2Se |
| Molar mass |
168.07 g·mol−1 |
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)[2] is the 21st proteinogenic amino acid.
Selenocysteine exists naturally in all three domains of life, but not in every lineage, as a building block of selenoproteins.[3] 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[4] at the National Institutes of Health.
Contents
- 1 Structure
- 2 Biology
- 3 Applications
- 4 See also
- 5 References
- 6 Further reading
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. (Like other natural proteinogenic amino acids, cysteine and selenocysteine have L chirality in the older D/L notation based on homology to D and L glyceraldehyde. 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 sulfur (resp. 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 one or more selenocysteine residues are called selenoproteins. Most selenoproteins contain a single selenocysteine residue. Selenoproteins which depend on selenocysteine's catalytic activity are called selenoenzymes.[5] Selenoenzymes have been found to employ catalytic triad structures that influence the nucleophilicity of the active site selenocysteine.[citation needed]
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.[6]
Although it is found in the three domains of life, it is not universal in all organisms.[7] Unlike other amino acids present in biological proteins, selenocysteine is not coded for directly in the genetic code.[8] 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[9] and its efficiency depends on the selenoprotein being synthesized and on translation initiation factors.[10] 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.[11] 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.[12]
Again unlike the other amino acids, no free pool of selenocysteine exists in the cell. Its high reactivity would cause damage to cells.[original research?] 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, tRNASec, 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-tRNASec 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. In eukaryotes and archaea, two enzymes are required to convert tRNA-bound seryl residue into tRNA selenocysteinyl residue: PSTK [O-phosphoseryl-tRNA[Ser]Sec kinase]) and selenocysteine synthase.[13][14] Finally, the resulting Sec-tRNASec 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 2016, fifty-four human proteins are known to contain selenocysteine (selenoproteins).[15]
Selenocysteine derivatives γ-glutamyl-Se-methylselenocysteine and Se-methylselenocysteine occur naturally in plants of the genera Allium and Brassica.[16]
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 multiwavelength 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.[3]
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.
References
- ^ Merck Index, 12th Edition, 8584
- ^ "IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature Committee of IUBMB (NC-IUBMB)" (PDF). European Journal of Biochemistry. 264 (2): 607–609. 17 August 1999. doi:10.1046/j.1432-1327.1999.news99.x.
- ^ a b Johansson, L.; Gafvelin, G.; Amér, E. S. J. (30 October 2005). "Selenocysteine in Proteins — Properties and Biotechnological Use". Biochimica et Biophysica Acta. 1726 (1): 1–13. doi:10.1016/j.bbagen.2005.05.010. (Subscription required (help)).
- ^ Stadtman, Therese (Mar 8, 1974). "Selenium Biochemistry". Science. 183 (4128): 915–22. Bibcode:1974Sci...183..915S. doi:10.1126/science.183.4128.915. PMID 4605100.
- ^ Roy, G.; Sarma, B. K.; Phadnis, P.P.; Mugesh, G. (2005). "Selenium-containing enzymes in mammals: chemical perspectives". Journal of Chemical Sciences. 117 (4): 287–303. doi:10.1007/BF02708441.
- ^ Byun, B. J.; Kang, Y. K. (2011). "Conformational Preferences and pKa Value of Selenocysteine Residue". Biopolymers. 95 (5): 345–353. doi:10.1002/bip.21581. PMID 21213257.
- ^ Longtin, R (2004). "A forgotten debate: Is selenocysteine the 21st amino acid?" (PDF). Journal of the National Cancer Institute. 96 (7): 504–5. doi:10.1093/jnci/96.7.504. PMID 15069108.
- ^ Böck A.; Forchhammer, K.; Heider, J.; Baron, C. (1991). "Selenoprotein Synthesis: An Expansion of the Genetic Code". Trends in Biochemical Sciences. 16 (12): 463–467. doi:10.1016/0968-0004(91)90180-4. PMID 1838215.
- ^ Baranov P. V.; Gesteland R. F.; Atkins, J. F. (2002). "Recoding: Translational Bifurcations in Gene Expression". Gene. 286 (5): 187–201. doi:10.1016/S0378-1119(02)00423-7. PMID 11943474.
- ^ Donovan, J.; Copeland, P. R. (2010). "The Efficiency of Selenocysteine Incorporation is Regulated by Translation Initiation Factors". Journal of Molecular Biology. 400 (4): 659–664. doi:10.1016/j.jmb.2010.05.026. PMC 3721751 . PMID 20488192.
- ^ Atkins, J. F. (2009). Recoding: Expansion of Decoding Rules Enriches Gene Expression. Springer. p. 31. ISBN 978-0-387-89381-5.
- ^ Berry, M. J.; Banu, L.; Harney, J. W.; Larsen, P. R. (1993). "Functional Characterization of the Eukaryotic SECIS Elements which Direct Selenocysteine Insertion at UGA Codons" (PDF). The EMBO Journal. 12 (8): 3315–3322. PMC 413599 . PMID 8344267.
- ^ Xu, Xue-Ming; Carlson, Bradley A; Mix, Heiko; Zhang, Yan; Saira, Kazima; Glass, Richard S; Berry, Marla J; Gladyshev, Vadim N; Hatfield, Dolph L. "Biosynthesis of Selenocysteine on Its tRNA in Eukaryotes". PLoS Biology. 5 (1): e4. doi:10.1371/journal.pbio.0050004. PMC 1717018 . PMID 17194211.
- ^ Yuan, Jing; Palioura, Sotiria; Salazar, Juan Carlos; Su, Dan; O'Donoghue, Patrick; Hohn, Michael J.; Cardoso, Alexander Machado; Whitman, William B.; Söll, Dieter (2006-12-12). "RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea". Proceedings of the National Academy of Sciences. 103 (50): 18923–18927. doi:10.1073/pnas.0609703104. ISSN 0027-8424. PMC 1748153 . PMID 17142313.
- ^ Romagné, Frédéric; Santesmasses, Didac; White, Louise; Sarangi, Gaurab K.; Mariotti, Marco; Hübler, Ron; Weihmann, Antje; Parra, Genís; Gladyshev, Vadim N. (2014-01-01). "SelenoDB 2.0: annotation of selenoprotein genes in animals and their genetic diversity in humans". Nucleic Acids Research. 42 (D1): D437–D443. doi:10.1093/nar/gkt1045. ISSN 0305-1048. PMC 3965025 . PMID 24194593. Archived from the original on June 5, 2016.
- ^ Block, E. (2010). Garlic and Other Alliums: The Lore and the Science. Royal Society of Chemistry. ISBN 0-85404-190-7.
Further reading
- Zinoni, F.; Birkmann, A.; Stadtman, T. C.; Bock, A. (1986). "Nucleotide Sequence and Expression of the Selenocysteine-Containing Polypeptide of Formate Dehydrogenase (Formate-Hydrogen-Lyase-Linked) from Escherichia coli". PNAS. 83 (13): 4650–4654. Bibcode:1986PNAS...83.4650Z. doi:10.1073/pnas.83.13.4650. PMC 323799 . PMID 2941757.
- Zinoni, F.; Birkmann, A.; Leinfelder, W.; Bock, A. (1987). "Cotranslational Insertion of Selenocysteine into Formate Dehydrogenase from Escherichia coli Directed by a UGA Codon". PNAS. 84 (10): 3156–3160. Bibcode:1987PNAS...84.3156Z. doi:10.1073/pnas.84.10.3156. PMC 304827 . PMID 3033637.
- Cone, B. E.; del Rio, R. M.; Davis, J. N.; Stadtman, T. C. (1976). "Chemical Characterization of the Selenoprotein Component of Clostridial Glycine Reductase: Identification of Selenocysteine as the Organoselenium Moiety". PNAS. 73 (8): 2659–2663. Bibcode:1976PNAS...73.2659C. doi:10.1073/pnas.73.8.2659. PMC 430707 . PMID 1066676.
- Fenyö, D.; Beavis, R.C. (2015). "Selenocysteine: Wherefore Art Thou?". J Proteome Res. doi:10.1021/acs.jproteome.5b01028. PMID 26680273.
|
Selenium compounds
|
| Se(0,I) |
|
| Se(I) |
|
| Se(II) |
- SeS2
- Ag2Se
- Al2Se3
- CaSe
- Se2-
|
| Se(IV) |
- SeCl4
- SeF4
- SeO2
- SeS2
- SeOBr2
- SeOCl2
|
| Se(VI) |
|
