This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Individual Amino Acids Biosynthesis → Selenocysteine Biosynthesis|
Se0 is an essential trace element for many (but not all) organisms from all domains of life. For example among animals, mammals require selenium but some protists, such as Trypanosoma brucei, do not [Aeby09]. The green alga Chlamydomonas reinhardii contains selenoproteins, but land plants and yeast do not [Novoselov02]. The best studied biological form of Se0 is the amino acid L-selenocysteine (sec). The compound display pages for Se0 and L-selenocysteine show links to enzymes in MetaCyc for which Se0 is functionally important. In addition, see EC 220.127.116.11, EC 18.104.22.168, EC 22.214.171.124 and EC 126.96.36.199. Se0 is also present in selenonucleosides that have been identified in bacterial tRNAs. Reviewed in [Stock09].
In L-selenocysteine the thiol group of L-cysteine is replaced by a selenol group. L-selenocysteine is considered to be the 21st genetically encoded amino acid because it is co-translationally inserted into nacent polypeptide chains at an in-frame UGA nonsnense codon in the mRNA. This is done by a decoding mechanism that involves a selenocysteine insertion sequence (SECIS) element in the mRNA and coordinated interactions between RNA-protein complexes. A model for the role of these cytoplasmic and nuclear supramolecular complex interactions in L-selenocysteine biosynthesis has been proposed [SmallHoward06]. The function of L-selenocysteine in proteins remains to be completely defined, although its occurrence in the active site of some redox-active enzymes suggests a role in their catalytic mechanism. There are two known pathways for selenocysteine biosynthesis. One is found in bacteria (see pathway selenocysteine biosynthesis I (bacteria)) and the other is found in archaea and eukaryotes (this pathway), which has interesting phylogenetic implications. Reviewed in [Stock09].
About This Pathway
The pathway shown here is found in some archaea and eukaryotes, the best studied organisms being certain methanogens, and mammals [Xu07b]. It is an indirect, tRNA-dependent pathway for amino acid biosynthesis in which the amino acid is synthesized on its tRNA. A non-cognate amino acid is first attached to the tRNA and is then converted to the cognate amino acid by tRNA-dependent modifying enzymes. Other examples of an indirect, tRNA-dependent amino acid biosynthetic pathway are asparagine biosynthesis III (tRNA-dependent) and L-glutamine biosynthesis II (tRNA-dependent) (as compared with tRNA charging).
The difference between this pathway and the bacterial L-selenocysteine biosynthetic pathway (selenocysteine biosynthesis I (bacteria)) is that in bacteria L-seryl-tRNAsec is directly converted to L-selenocysteinyl-tRNAsec, whereas in archaea and eukaryotes L-seryl-tRNAsec is first converted to O-phospho-L-seryl-tRNASec by a kinase and the O-phosphoserine-containing product is transformed to L-selenocysteine by SepSecS. In both pathways, selenophosphate is the Se0 donor, synthesized from hydrogen selenide and ATP by selenophosphate synthetase (in [Xu07c]). Reviewed in [Stock09, Sheppard08, Xu07a].
In this pathway of L-selenocysteine biosynthesis on tRNAsec, tRNAsec is charged with L-serine. The seryl moiety of the L-seryl-tRNAsec formed is phosphorylated by O-phosphoseryl-tRNAsec kinase to form an O-phospho-L-seryl-tRNASec intermediate which is then modified to L-selenocysteinyl-tRNAsec by O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase. Thus, the backbone for L-selenocysteine is L-serine. Although the pathway is identical in archaea and eukaryota, a difference between them in tRNAsec identity elements for the phosphorylation reaction has been found. Reviewed in [Sheppard08, Xu07a].
The seryl-tRNA synthetase step in this pathway is shared among bacteria, archaea and eukaryota. However, this pathway then diverges from the bacterial pathway. In the bacterial L-selenocysteine biosynthetic pathway selenocysteine synthase converts L-seryl-tRNAsec to L-selenocysteinyl-tRNAsec and L-selenocysteine is incorporated into proteins using an RNA element that facilitates UGA recognition and the selenocysteine-specific elongation factor SelB (see pathway selenocysteine biosynthesis I (bacteria)). In this archaeal and eukaryotic pathway L-seryl-tRNAsec is first converted to O-phospho-L-seryl-tRNASec by O-phosphoseryl-tRNAsec kinase and the bound 3-phospho-L-serine is converted to L-selenocysteine by O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase using selenophosphate. Reviewed in [Sheppard08, Xu07a].
Variants: selenocysteine biosynthesis I (bacteria)
Relationship Links: KEGG:PART-OF:map00970
Aeby09: Aeby E, Palioura S, Pusnik M, Marazzi J, Lieberman A, Ullu E, Soll D, Schneider A (2009). "The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes." Proc Natl Acad Sci U S A 106(13);5088-92. PMID: 19279205
Baron90: Baron C, Heider J, Bock A (1990). "Mutagenesis of selC, the gene for the selenocysteine-inserting tRNA-species in E. coli: effects on in vivo function." Nucleic Acids Res 18(23);6761-6. PMID: 1702199
Novoselov02: Novoselov SV, Rao M, Onoshko NV, Zhi H, Kryukov GV, Xiang Y, Weeks DP, Hatfield DL, Gladyshev VN (2002). "Selenoproteins and selenocysteine insertion system in the model plant cell system, Chlamydomonas reinhardtii." EMBO J 21(14);3681-93. PMID: 12110581
SmallHoward06: Small-Howard A, Morozova N, Stoytcheva Z, Forry EP, Mansell JB, Harney JW, Carlson BA, Xu XM, Hatfield DL, Berry MJ (2006). "Supramolecular complexes mediate selenocysteine incorporation in vivo." Mol Cell Biol 26(6);2337-46. PMID: 16508009
Xu07a: Xu XM, Carlson BA, Zhang Y, Mix H, Kryukov GV, Glass RS, Berry MJ, Gladyshev VN, Hatfield DL (2007). "New developments in selenium biochemistry: selenocysteine biosynthesis in eukaryotes and archaea." Biol Trace Elem Res 119(3);234-41. PMID: 17916946
Xu07c: Xu XM, Carlson BA, Irons R, Mix H, Zhong N, Gladyshev VN, Hatfield DL (2007). "Selenophosphate synthetase 2 is essential for selenoprotein biosynthesis." Biochem J 404(1);115-20. PMID: 17346238
Araiso08: Araiso Y, Palioura S, Ishitani R, Sherrer RL, O'Donoghue P, Yuan J, Oshikane H, Domae N, Defranco J, Soll D, Nureki O (2008). "Structural insights into RNA-dependent eukaryal and archaeal selenocysteine formation." Nucleic Acids Res 36(4);1187-99. PMID: 18158303
Baron91: Baron C, Bock A (1991). "The length of the aminoacyl-acceptor stem of the selenocysteine-specific tRNA(Sec) of Escherichia coli is the determinant for binding to elongation factors SELB or Tu." J Biol Chem 266(30);20375-9. PMID: 1939093
Bilokapic04: Bilokapic S, Korencic D, Soll D, Weygand-Durasevic I (2004). "The unusual methanogenic seryl-tRNA synthetase recognizes tRNASer species from all three kingdoms of life." Eur J Biochem 271(4);694-702. PMID: 14764085
Carlson04: Carlson BA, Xu XM, Kryukov GV, Rao M, Berry MJ, Gladyshev VN, Hatfield DL (2004). "Identification and characterization of phosphoseryl-tRNA[Ser]Sec kinase." Proc Natl Acad Sci U S A 101(35);12848-53. PMID: 15317934
Costa00: Costa M, Rodriguez-Sanchez JL, Czaja AJ, Gelpi C (2000). "Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP(Ser)Sec complex recognized by autoantibodies from patients withtype-1 autoimmune hepatitis." Clin Exp Immunol 121(2);364-74. PMID: 10931155
Ehrenreich92: Ehrenreich A, Forchhammer K, Tormay P, Veprek B, Bock A (1992). "Selenoprotein synthesis in E. coli. Purification and characterisation of the enzyme catalysing selenium activation." Eur J Biochem 206(3);767-73. PMID: 1606960
Ganichkin08: Ganichkin OM, Xu XM, Carlson BA, Mix H, Hatfield DL, Gladyshev VN, Wahl MC (2008). "Structure and catalytic mechanism of eukaryotic selenocysteine synthase." J Biol Chem 283(9);5849-65. PMID: 18093968
Guimaraes96: Guimaraes MJ, Peterson D, Vicari A, Cocks BG, Copeland NG, Gilbert DJ, Jenkins NA, Ferrick DA, Kastelein RA, Bazan JF, Zlotnik A (1996). "Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: is there an autoregulatory mechanism in selenocysteine metabolism?." Proc Natl Acad Sci U S A 93(26);15086-91. PMID: 8986768
Kaiser05: Kaiser JT, Gromadski K, Rother M, Engelhardt H, Rodnina MV, Wahl MC (2005). "Structural and functional investigation of a putative archaeal selenocysteine synthase." Biochemistry 44(40);13315-27. PMID: 16201757
Kim92: Kim IY, Veres Z, Stadtman TC (1992). "Escherichia coli mutant SELD enzymes. The cysteine 17 residue is essential for selenophosphate formation from ATP and selenide." J Biol Chem 267(27);19650-4. PMID: 1527085
Kim93: Kim IY, Veres Z, Stadtman TC (1993). "Biochemical analysis of Escherichia coli selenophosphate synthetase mutants. Lysine 20 is essential for catalytic activity and cysteine 17/19 for 8-azido-ATP derivatization." J Biol Chem 1993;268(36);27020-5. PMID: 8262938
Kim95: Kim IY, Stadtman TC (1995). "Selenophosphate synthetase: detection in extracts of rat tissues by immunoblot assay and partial purification of the enzyme from the archaean Methanococcus vannielii." Proc Natl Acad Sci U S A 92(17);7710-3. PMID: 7644481
Lacourciere99: Lacourciere GM, Stadtman TC (1999). "Catalytic properties of selenophosphate synthetases: comparison of the selenocysteine-containing enzyme from Haemophilus influenzae with the corresponding cysteine-containing enzyme from Escherichia coli." Proc Natl Acad Sci U S A 96(1);44-8. PMID: 9874769
Leinfelder88: Leinfelder W, Zehelein E, Mandrand-Berthelot MA, Bock A (1988). "Gene for a novel tRNA species that accepts L-serine and cotranslationally inserts selenocysteine." Nature 331(6158);723-5. PMID: 2963963
Liu97: Liu SY, Stadtman TC (1997). "Selenophosphate synthetase: enzyme labeling studies with [gamma-32P]ATP, [beta-32P]ATP, [8-14C]ATP, and [75Se]selenide." Arch Biochem Biophys 341(2);353-9. PMID: 9169026
Preabrazhenskay09: Preabrazhenskaya YV, Kim IY, Stadtman TC (2009). "Binding of ATP and its derivatives to selenophosphate synthetase from Escherichia coli." Biochemistry (Mosc) 74(8);910-6. PMID: 19817692
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