Selenocysteine: Difference between revisions

{{cs1 config|name-list-style=vanc}}

| Watchedfields = changed

| verifiedrevid = 458287647

| Reference = <ref>''[[Merck Index]]'', 12th Edition, '''8584'''</ref>

| ImageFile = L-selenocysteine-2D-skeletal.png

| ImageFile1 = Selenocysteine-3D-vdW.png

| IUPACName = Selenocysteine

| SystematicName = 3-Selanyl-<small>L</small>-alanine <small>''(semisystematic name)''</small>

<br>2-Amino-3-selanylpropanoic acid <small>''(fully systematic name)''</small>

| OtherNames = <small>L</small>-Selenocysteine; Selenium-cysteine

| Section1 = {{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| CASNo = 3614-08-2

| PubChem = 25076

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 0CH9049VIS

| SMILES1 = O=C([O-])[C@@H]([NH3+])C[SeH]

| SMILES1_Comment = [[Zwitterion]]

| Section2 = {{Chembox Properties

| C=3 | H=7 | N=1 | O=2 | Se=1

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

| Solubility =

| Section3 = {{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt =

}}

| Section4 = {{Chembox Properties

|pKa=5.24,<ref name="HuberCriddle">{{Cite journal |last1=Huber |first1=R. E. |last2=Criddle |first2=R. S. |date=1967-10-01 |title=Comparison of the chemical properties of selenocysteine and selenocystine with their sulfur analogs |url=https://dx.doi.org/10.1016/0003-9861%2867%2990136-1 |journal=Archives of Biochemistry and Biophysics |volume=122 |issue=1 |pages=164–173 |doi=10.1016/0003-9861(67)90136-1 |pmid=6076213 |issn=0003-9861}}</ref> 5.43<ref name="Sec pKA">{{Cite journal |last1=Thapa |first1=Bishnu |last2=Schlegel |first2=H. Bernhard |date=2016-11-10 |title=Theoretical Calculation of p K a 's of Selenols in Aqueous Solution Using an Implicit Solvation Model and Explicit Water Molecules |url=https://pubs.acs.org/doi/10.1021/acs.jpca.6b09520 |journal=The Journal of Physical Chemistry A |language=en |volume=120 |issue=44 |pages=8916–8922 |doi=10.1021/acs.jpca.6b09520 |pmid=27748600 |bibcode=2016JPCA..120.8916T |issn=1089-5639}}</ref>

'''Selenocysteine''' (symbol '''Sec''' or '''U''',<ref>{{cite web| url = http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | title = Nomenclature and Symbolism for Amino Acids and Peptides | publisher = IUPAC-IUB Joint Commission on Biochemical Nomenclature | year = 1983 | access-date = 5 March 2018| archive-url= https://web.archive.org/web/20081009023202/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html| archive-date= 9 October 2008 | url-status= live}}</ref> in older publications also as '''Se-Cys''')<ref>{{cite journal|date=17 August 1999|title=IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature Committee of IUBMB (NC-IUBMB)|journal=[[Eur. J. Biochem.|European Journal of Biochemistry]]|volume=264|issue=2|pages=607–609|doi=10.1046/j.1432-1327.1999.news99.x}}</ref> is the 21st [[proteinogenic amino acid]]. [[Selenoproteins]] contain selenocysteine residues. Selenocysteine is an analogue of the more common [[cysteine]] with [[selenium]] in place of the [[sulfur]].

Selenocysteine is present in several [[enzyme]]s (for example [[glutathione peroxidase]]s, [[tetraiodothyronine 5 deiodinase|tetraiodothyronine 5′ deiodinases]], [[thioredoxin reductase]]s, [[formate dehydrogenase]]s, [[glycine reductase]]s, [[selenophosphate synthetase 2]], methionine-''R''-sulfoxide reductase B1 ([[SEPX1]]), and some [[hydrogenase]]s). It occurs in all three [[Domain (biology)|domains of life]], including important enzymes (listed above) present in humans.<ref name="Johansson">{{cite journal | vauthors = Johansson L, Gafvelin G, Arnér ES | title = Selenocysteine in proteins—properties and biotechnological use | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1726 | issue = 1 | pages = 1–13 | date = October 2005 | pmid = 15967579 | doi = 10.1016/j.bbagen.2005.05.010 | hdl = 10616/39311 | hdl-access = free }}</ref>

Selenocysteine was discovered in 1974<ref>{{Cite web |title=Stadtman Pioneer of Selenium Biochemistry - Office of NIH History and Stetten Museum |url=https://history.nih.gov/display/history/Stadtman+Pioneer+of+Selenium+Biochemistry |access-date=2023-04-06 |website=history.nih.gov}}</ref> by biochemist [[Thressa Stadtman]] at the [[National Institutes of Health]].<ref>{{cite journal | vauthors = Stadtman TC | title = Selenium biochemistry | journal = Science | volume = 183 | issue = 4128 | pages = 915–22 | date = March 1974 | pmid = 4605100 | doi = 10.1126/science.183.4128.915 | bibcode = 1974Sci...183..915S | s2cid = 84982102 }}</ref>

==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.<ref>{{ cite journal | title = Crystal structure of seleno-L-cystine dihydrochloride | first1 = C. H. | last1 = Görbitz | first2 = V. | last2 = Levchenko | first3 = J. | last3 = Semjonovs | first4 = M. Y. | last4 = Sharif | journal = [[Acta Crystallographica Section E]] | year = 2015 | volume = 71 | issue = 6 | pages = 726–729 | doi = 10.1107/S205698901501021X | pmid = 26090162 | pmc = 4459342 | bibcode = 2015AcCrE..71..726G }}</ref> Both selenocysteine and selenocystine are white solids. The Se-H group is more acidic ([[pKa|p''K''_a]] = 5.43<ref name="Sec pKA"/>) than the thiol group; thus, it is [[deprotonated]] at physiological [[pH]].<ref>{{cite journal | vauthors = Reich HJ, Hondal RJ | title = Why nature chose selenium | journal = ACS Chemical Biology | volume = 11 | issue = 4 | pages = 821–841 | date = April 2016 | pmid = 26949981 | doi = 10.1021/acschembio.6b00031 }}</ref>

== Structure ==

Selenocysteine has the same structure as [[cysteine]], but with an atom of [[selenium]] taking the place of the usual sulfur. It has a [[selenol]] group. Like other natural proteinogenic amino acids, cysteine and selenocysteine have {{small|L}} [[chirality]] in the older {{small|D}}/{{small|L}} notation based on homology to {{small|D}}- and {{small|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 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]]s. Most selenoproteins contain a single selenocysteine residue. Selenoproteins that exhibit catalytic activity are called selenoenzymes.<ref>{{cite journal | vauthors = Roy G, Sarma BK, Phadnis PP, Mugesh G | title = Selenium-containing enzymes in mammals: chemical perspectives | journal = [[Journal of Chemical Sciences]] | year = 2005 | volume = 117 | issue = 4 | pages = 287–303 | doi = 10.1007/BF02708441 | s2cid = 32351033 |url=http://repository.ias.ac.in/79332/1/53-PUB.pdf | doi-access = free }}</ref>

== Biology ==

Selenocysteine has a lower [[reduction potential]] than cysteine. These properties make it very suitable in proteins that are involved in [[antioxidant]] activity.<ref>{{cite journal | vauthors = Byun BJ, Kang YK | title = Conformational preferences and pK(a) value of selenocysteine residue | journal = Biopolymers | volume = 95 | issue = 5 | pages = 345–53 | date = May 2011 | pmid = 21213257 | doi = 10.1002/bip.21581 | s2cid = 11002236 }}</ref>

Although it is found in the [[Three-domain system|three domains of life]], it is not universal in all organisms.<ref>{{cite journal | vauthors = Longtin R | title = A forgotten debate: is selenocysteine the 21st amino acid? | journal = Journal of the National Cancer Institute | volume = 96 | issue = 7 | pages = 504–5 | date = April 2004 | pmid = 15069108 | doi = 10.1093/jnci/96.7.504 | doi-access = free }}</ref> Unlike other amino acids present in biological [[protein]]s, selenocysteine is not coded for directly in the [[genetic code]].<ref>{{cite journal | vauthors = Böck A, Forchhammer K, Heider J, Baron C | title = Selenoprotein synthesis: an expansion of the genetic code | journal = Trends in Biochemical Sciences | volume = 16 | issue = 12 | pages = 463–7 | date = December 1991 | pmid = 1838215 | doi = 10.1016/0968-0004(91)90180-4 }}</ref> Instead, it is encoded in a special way by a UGA [[codon]], which is normally the "opal" [[stop codon]]. Such a mechanism is called translational [[Recoding (biology)|recoding]]<ref>{{cite journal | vauthors = Baranov PV, Gesteland RF, Atkins JF | title = Recoding: translational bifurcations in gene expression | journal = Gene | volume = 286 | issue = 2 | pages = 187–201 | date = March 2002 | pmid = 11943474 | doi = 10.1016/S0378-1119(02)00423-7 | s2cid = 976337 }}</ref> and its efficiency depends on the selenoprotein being synthesized and on translation [[initiation factor]]s.<ref>{{cite journal | vauthors = Donovan J, Copeland PR | title = The efficiency of selenocysteine incorporation is regulated by translation initiation factors | journal = Journal of Molecular Biology | volume = 400 | issue = 4 | pages = 659–64 | date = July 2010 | pmid = 20488192 | pmc = 3721751 | doi = 10.1016/j.jmb.2010.05.026 }}</ref> 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 [[SECIS element|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.<ref>{{cite book | author = Atkins, J. F. | title = Recoding: Expansion of Decoding Rules Enriches Gene Expression | year = 2009 | page = 31 | publisher = Springer | isbn = 978-0-387-89381-5 | url = https://books.google.com/books?id=8cSZpPWXoqIC&pg=PA31 }}</ref> In [[Archaea]] and in [[eukaryote]]s, the SECIS element is in the [[3' UTR|3′ untranslated region]] (3′ UTR) of the mRNA and can direct multiple UGA codons to encode selenocysteine residues.<ref>{{cite journal | vauthors = Berry MJ, Banu L, Harney JW, Larsen PR | title = Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons | journal = The EMBO Journal | volume = 12 | issue = 8 | pages = 3315–22 | date = August 1993 | pmid = 8344267 | pmc = 413599 | doi = 10.1002/j.1460-2075.1993.tb06001.x }}</ref>

Unlike the other amino acids, no free pool of selenocysteine exists in the cell. Its high reactivity would cause damage to cells.<ref>{{Cite journal |last=Spallholz |first=Julian E. |date=July 1994 |title=On the nature of selenium toxicity and carcinostatic activity |url=https://linkinghub.elsevier.com/retrieve/pii/0891584994900078 |journal=Free Radical Biology and Medicine |language=en |volume=17 |issue=1 |pages=45–64 |doi=10.1016/0891-5849(94)90007-8|pmid=7959166 }}</ref> Instead, cells store selenium in the less reactive oxidized form, selenocystine, or in methylated form, selenomethionine. 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-pair (bacteria) or 10-base-pair (eukaryotes){{fix|text=Archaea?}} acceptor stem, a long variable region arm, and substitutions at several well-conserved base positions. The selenocysteine tRNAs are initially charged with serine by [[serine—tRNA ligase|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, [[eEF-1|eEF1A]] in eukaryotes).{{fix|text=Archaea?}}

Rather, the tRNA-bound seryl residue is converted to a selenocysteine residue by the [[pyridoxal phosphate]]-containing enzyme [[L-seryl-tRNASec selenium transferase|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.<ref>{{cite journal | vauthors = Xu XM, Carlson BA, Mix H, Zhang Y, Saira K, Glass RS, Berry MJ, Gladyshev VN, Hatfield DL | title = Biosynthesis of selenocysteine on its tRNA in eukaryotes | journal = PLOS Biology | volume = 5 | issue = 1 | pages = e4 | date = January 2007 | pmid = 17194211 | pmc = 1717018 | doi = 10.1371/journal.pbio.0050004 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yuan J, Palioura S, Salazar JC, Su D, O'Donoghue P, Hohn MJ, Cardoso AM, Whitman WB, Söll D | title = RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 50 | pages = 18923–7 | date = December 2006 | pmid = 17142313 | pmc = 1748153 | doi = 10.1073/pnas.0609703104 | bibcode = 2006PNAS..10318923Y | doi-access = free }}</ref> 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 ([[SECISBP2|SBP2]] for eukaryotic mSelB/eEFSec){{fix|text=Archaea?}} 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 <small>L</small>-[[alanine]] and selenide.<ref>{{cite journal | vauthors = Labunskyy VM, Hatfield DL, Gladyshev VN | title = Selenoproteins: molecular pathways and physiological roles | journal = Physiological Reviews | volume = 94 | issue = 3 | pages = 739–77 | date = July 2014 | pmid = 24987004 | pmc = 4101630 | doi = 10.1152/physrev.00039.2013 }}</ref>

{{As of|2021}}, 136 human proteins (in 37 families) are known to contain selenocysteine (selenoproteins).<ref>{{cite journal |vauthors=Romagné F, Santesmasses D, White L, Sarangi GK, Mariotti M, Hübler R, Weihmann A, Parra G, Gladyshev VN, Guigó R, Castellano S |date=January 2014 |title=SelenoDB 2.0: annotation of selenoprotein genes in animals and their genetic diversity in humans |journal=Nucleic Acids Research |volume=42 |issue=Database issue |pages=D437-43 |doi=10.1093/nar/gkt1045 |pmc=3965025 |pmid=24194593}} [http://selenodb.crg.eu/cgi-perl/advanced_search.pl?feature=protein&species=Homo+sapiens]</ref>

Selenocysteine derivatives γ-glutamyl-''Se''-methylselenocysteine and [[Se-methylselenocysteine|''Se''-methylselenocysteine]] occur naturally in plants of the genera ''[[Allium]]'' and ''[[Brassica]]''.<ref>{{cite book|author=Block, E.|title=Garlic and Other Alliums: The Lore and the Science|url=https://books.google.com/books?id=6AB89RHV9ucC|publisher=Royal Society of Chemistry|year=2010|isbn=978-0-85404-190-9}}</ref>

== 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 [[radiolabel]]ing, 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 {{sfrac|1|2}} and can be used for high-resolution [[NMR]], among others.<ref name="Johansson" />

== 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 ==

{{Reflist|33em}}

== Further reading ==

{{refbegin}}

* {{cite journal | vauthors = Zinoni F, Birkmann A, Stadtman TC, Böck A | title = Nucleotide sequence and expression of the selenocysteine-containing polypeptide of formate dehydrogenase (formate-hydrogen-lyase-linked) from Escherichia coli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 83 | issue = 13 | pages = 4650–4 | date = July 1986 | pmid = 2941757 | pmc = 323799 | doi = 10.1073/pnas.83.13.4650 | bibcode = 1986PNAS...83.4650Z | doi-access = free }}

* {{cite journal | vauthors = Zinoni F, Birkmann A, Leinfelder W, Böck A | title = Cotranslational insertion of selenocysteine into formate dehydrogenase from Escherichia coli directed by a UGA codon | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 10 | pages = 3156–60 | date = May 1987 | pmid = 3033637 | pmc = 304827 | doi = 10.1073/pnas.84.10.3156 | bibcode = 1987PNAS...84.3156Z | doi-access = free }}

* {{cite journal | vauthors = Cone JE, Del Río RM, Davis JN, Stadtman TC | title = Chemical characterization of the selenoprotein component of clostridial glycine reductase: identification of selenocysteine as the organoselenium moiety | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 8 | pages = 2659–63 | date = August 1976 | pmid = 1066676 | pmc = 430707 | doi = 10.1073/pnas.73.8.2659 | bibcode = 1976PNAS...73.2659C | doi-access = free }}

* {{cite journal | vauthors = Fenyö D, Beavis RC | title = Selenocysteine: Wherefore Art Thou? | journal = Journal of Proteome Research | volume = 15 | issue = 2 | pages = 677–8 | date = February 2016 | pmid = 26680273 | doi = 10.1021/acs.jproteome.5b01028 }}

{{refend}}

== External links ==

{{Scholia|topic}}

* [https://ciencia.ladiaria.com.uy/articulo/2019/2/cientifico-uruguayo-halla-por-primera-vez-en-hongos-el-aminoacido-selenocisteina/ For the first time a Uruguayan scientist finds selenocysteine in fungi] {{Webarchive|url=https://web.archive.org/web/20190222133330/https://ciencia.ladiaria.com.uy/articulo/2019/2/cientifico-uruguayo-halla-por-primera-vez-en-hongos-el-aminoacido-selenocisteina/ |date=2019-02-22 }} {{in lang|es}}

{{Amino acids}}

{{selenium compounds}}

[[Category:Alpha-Amino acids]]

[[Category:Proteinogenic amino acids]]

[[Category:Selenols]]