Selenocysteine metabolism

Selenocysteine (SEC; one letter abbreviation: U) is the 21st amino acid encoded by UGA codon. This amino acid is rarely present in proteins called selenoproteins. Selenocysteine is analogous to cysteine and the sulphur residue is replaced by a selenium residue. Selenocysteine have lower pKa and higher reduction potential than cysteine providing the enzymes’ redox centres with increased catalytic efficiency [1]. As UGA is a stop codon, UGA coding Selenocysteine is identified with a stem-loop structure called SElenoCysteine Insertion sequence (SECIS). SECIS is present in the 3’ untranslated region of selenoprotein genes [2]. The four nucleotide AUGA segment of eukaryotic canonical SECIS element is previously considered invariant. In addition to it, noncanonical SECIS element with GGGA sequence was identified in Toxoplasma gondii and Neospora caninum. The analysis of EST sequences of T. gondii and N. caninum by Novoselov et al has suggested the presence of selenoprotein homologues of Sel S, Sel W, Sel T, Sel K and Sel Q in T. gondii and the first three in N. caninum [3]. Of these, Sel Q, Sel K and Sel S and SEL T are identified in N. caninum gene models in ToxoDB. Of these, Sel T is missing in T. gondii gene models. The comparison of gene models in ToxoDB to the predicted protein sequences in [3] showed that these selenocysteine-specific UGA codons are either considered as stop codons (TGME49_116600, TGME49_073770, TGME49_112640) or as part of intron (NCLIV_041980) in gene models.

The four-nucleotide segment AUGA/GGGA of SECIS is important for the interaction with SECIS binding protein, SBP2, which is essential for the selenocysteine incorporation and translation of selenoprotein mRNAs [4, 5]. The SBP protein is not identified in N. caninum, T. gondii or Plasmodium falciparum genomes. UGA codon of selenocysteine is decoded by a specific elongation factor SelB in eubacteria and its mammalian homolog mSelB was also identified [6, 7]. SPB forms a complex with Selenocysteine-specific elongation factor and the SEC-specific tRNA and the interaction of this complex is essential for encoding UGA codon with selenocysteine [8]. Both tRNA^SEC and SEC-specific elongation factors are present in P. falciparum , N. caninum and T. gondii. Two other factors which regulate selenoprotein expression are soluble liver antigen (SLA) and SECp43. SLA has been demonstrated to be involved in interaction with tRNA^SEC [9] and selenophosphate synthase I (SPS1, also known as selenium, water dikinase) [10]. SECp43 interacts with all these factors including SLA and involved in regulation of cellular localisation of SLA and tRNA^SEC [9, 10]. SLA is present in genomes of Plasmodium species and T. gondii and N. caninum.

As selenoprotein biosynthesis is a metabolic capability present in both Plasmodium species and Coccidia, Selenocysteine biosynthesis pathway is also present in MPMP. The enzymes which are involved in the catalysis of selenate to selenide are not identified in P. falciparum. The analysis of KEGG database suggested that most of the reactions are spontaneous and the two enzyme catalysed reactions involved in the conversion of slenate to 3’-phosphoadenylyl selenate are catalysed by the enzymatic activities of 2.7.7.4 and 2.7.1.25. These enzymes catalyse the conversion of sulfate to 3’-phosphoadenylyl sulfate and can also catalyse the above mentioned reactions. The ortholog of human bifunctional 2.7.7.4/2.7.1.25 enzyme is also present in T. gondii and N. caninum genomes.

List of genes annotated as tRNA-SEC in N. caninum genome

Genes encoding selenoproteins present in the N. caninum genome

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Sources of metabolites