Selenocysteine: Difference between revisions
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Selenocysteine (Sec, U) is called the 21st [[Amino Acids|amino acid]]<ref name='21st'>PMID: 11028985</ref>. It is incorporated into rare proteins in all domains of life, and is essential for life. When the UGA stop codon is accompanied by a [[#Translation from UGA Stop Codon|suitable signal]], it is translated as Sec instead of stopping translation. For more information, see [http://en.wikipedia.org/wiki/Selenocysteine Selenocysteine in Wikipedia]. | <applet size='300' frame='true' align='right' caption='Selenocysteine' | ||
scene='Selenocysteine/Selenocysteine_dot_pdb/1' /> | |||
Selenocysteine ('''Sec, U'''), shown at right ( | |||
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<script>select all; spacefill;</script> | |||
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), is called the 21st [[Amino Acids|amino acid]]<ref name='21st'>PMID: 11028985</ref>. It is incorporated into rare proteins in all domains of life, and is essential for life. When the UGA stop codon is accompanied by a [[#Translation from UGA Stop Codon|suitable signal]], it is translated as Sec instead of stopping translation. In the [[PDB]], the code for [[Hetero atoms|hetero]] group Sec is '''SEC'''<ref>Prior to remediations of the [[wwPDB]] done after 2010, some Sec in the wwPDB was coded CSE.</ref>. For more information beyond what is below, please see [http://en.wikipedia.org/wiki/Selenocysteine Selenocysteine in Wikipedia]. | |||
==Importance== | ==Importance== | ||
Knockout of tRNA<sup>Sec</sup> in mice causes embryonic lethality<ref name='Palioura' />. This seems to fit with the [[#Occurrence|occurrence of Sec in several important enzymes]]. | |||
==Occurrence== | |||
Sec occurs in all domains of life, including bacteria, archaea, and eukaryota<ref>PMID: 19477234</ref><ref name'wp'>[http://en.wikipedia.org/wiki/Selenocysteine Selenocysteine in Wikipedia]</ref>. Sec occurs in the active sites of enzymes involved in removing reactive oxygen species, and in thyroid hormone activation<ref name='Palioura' />. For more examples, please see [http://en.wikipedia.org/wiki/Selenocysteine Selenocysteine in Wikipedia]. | |||
In January, 2022, '''76 entries''' in the [[wwPDB]] contain Sec. An example of naturally-occuring Sec is human glutathione peroxidase 4, where Sec46 occurs in the catalytic site. [[6hn3]] is the wild type, while [[6hkq]] has an inhibitor covalently bound to the Sec. | |||
==Visualization== | |||
[http://firstglance.jmol.org/fg.htm?mol=6hkq View 6HKQ in FirstGlance in Jmol]. | |||
:1. Look for the "Focus Box" (in the upper left panel, scroll down to the bottom ), and there click on "Find..". | |||
:2. Enter '''sec''' into the Find slot. | |||
To examine in detail what contacts the Sec46 (continuing from step 2 above): | |||
:3. Click on "Contacts & Non-Covalent Interactions" in the Tools tab. | |||
:4. Check "Atoms with Halos" as the target. | |||
:5. Click "Show atoms contacting target". | |||
Explore using the tools that are now available in the lower left "Contacts Shown" panel. | |||
==Translation from UGA Stop Codon== | ==Translation from UGA Stop Codon== | ||
During translation of mRNA, UGA is normally interpreted as a stop codon. However, when a special Sec-insertion stem-loop structure is present in the | During translation of mRNA, UGA is normally interpreted as a stop codon. However, when a special Sec-insertion sequence (SECIS), a stem-loop structure, is present downstream (in the untranslated region in mammals), UGA is translated as Sec<ref name='21st' /><ref name='Palioura' />. This involves the interaction of this stem-loop structure with specialized elongation factors called [[SelB]] in bacteria and EFSec in humans<ref name='Palioura' />. | ||
==Structure and Synthesis== | ==Structure and Synthesis== | ||
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Sec differs from the [[Amino Acids|20 standard amino acids]] because, in all domains of life, it lacks its own tRNA synthetase, and is synthesized from Ser covalently linked to tRNA<sup>Sec</sup>. | Sec differs from the [[Amino Acids|20 standard amino acids]] because, in all domains of life, it lacks its own tRNA synthetase, and is synthesized from Ser covalently linked to tRNA<sup>Sec</sup>. | ||
The [[X-ray crystallography|crystal]] structure of the complex that converts Ser-tRNA<sup>Sec</sup> to Sec-tRNA<sup>Sec</sup> ('''[[3hl2]]''') was | The [[X-ray crystallography|crystal]] structure of the complex that converts Ser-tRNA<sup>Sec</sup> to Sec-tRNA<sup>Sec</sup> ('''[[3hl2]]''') was reported in 2009<ref name='Palioura'>PMID: 19608919</ref>. This consists of ''O''-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) complexed to tRNA<sup>Sec</sup>, phosphoserine, and thiophosphate. The authors conclude that this structure, together with enzymology, supports a pyridoxal phosphate-dependent mechanism. | ||
==See Also== | |||
*[[Selenomethionine]] | |||
*[[Selenocysteine synthase]] | |||
*Selenocysteine-specific elongation factor [[SelB]] | |||
==Notes and References== | ==Notes and References== | ||
<references /> | <references /> | ||