Identification of Leishmania selenoproteins and SECIS element

Cassago, Alexandre; Rodrigues, Érico; Prieto, Evandro; Gaston, Kirk W.; Alfonzo, Juan D.; Iribar, M.P.; Berry, Marla J.; Cruz, Ângela K.; Thiemann, Otávio Henrique

doi:10.1016/j.molbiopara.2006.05.002

Cited by 40 publications

(43 citation statements)

References 22 publications

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“…This is consistent with earlier studies in Trypanosome where the presence of the three selenoproteins corresponding to the predicted molecular masses of the kinetoplastid homologs, SelK (9.5 kDa), SelT (28.8 kDa), and SelTryp (89 kDa) have been reported (10,12). Cassago et al (11) had earlier reported that the genes for glutathione peroxidase, selenoprotein R and selenoprotein SPS2 homologues in Leishmania have evolved into nonselenium-containing proteins.…”

Section: Discussionsupporting

confidence: 91%

“…The presence of selenoprotein and selenocysteine biosynthetic pathways has been reported in trypanosomes (10 -13). A survey of the Leishmania genome using the known selenoproteins as a search tool led to the identification of genes for glutathione peroxidase, selenoprotein R, and a selenoprotein SPS2 homolog (11). It was further reported that these selenoprotein homologs in Leishmania possess a Cys (UGU or UGC) residue at the equivalent position of Sec (UGA) (11).…”

mentioning

confidence: 99%

“…A survey of the Leishmania genome using the known selenoproteins as a search tool led to the identification of genes for glutathione peroxidase, selenoprotein R, and a selenoprotein SPS2 homolog (11). It was further reported that these selenoprotein homologs in Leishmania possess a Cys (UGU or UGC) residue at the equivalent position of Sec (UGA) (11). It was postulated that these homologs in Leishmania have evolved into nonselenium-containing proteins consistent with the loss of an identifiable SECIS element in their sequence (11).…”

mentioning

confidence: 99%

“…It was further reported that these selenoprotein homologs in Leishmania possess a Cys (UGU or UGC) residue at the equivalent position of Sec (UGA) (11). It was postulated that these homologs in Leishmania have evolved into nonselenium-containing proteins consistent with the loss of an identifiable SECIS element in their sequence (11). However, in another study, in silico analysis of the genomes of Trypanosoma and Leishmania for the occurrence of homologs of known selenoprotein genes, led to the identification of SelK and SelT, as well as a novel multidomain selenoprotein designated SelTryp (12).…”

mentioning

confidence: 99%

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Leishmania donovani Encodes a Functional Selenocysteinyl-tRNA Synthase

Manhas¹,

Gowri²,

Madhubala

2016

Journal of Biological Chemistry

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The synthesis of selenocysteine, the 21st amino acid, occurs on its transfer RNA (tRNA), tRNA Sec . tRNA Sec is initially aminoacylated with serine by seryl-tRNA synthetase and the resulting seryl moiety is converted to phosphoserine by O-phosphoseryl-tRNA kinase (PSTK) in eukaryotes. The selenium donor, selenophosphate is synthesized from selenide and ATP by selenophosphate synthetase. Selenocysteinyl-tRNA synthase (SepSecS) then uses the O-phosphoseryl-tRNA Sec and selenophosphate to form Sec-tRNA Sec in eukaryotes. Here, we report the characterization of selenocysteinyl-tRNA synthase from Leishmania donovani. Kinetoplastid SepSecS enzymes are phylogenetically closer to worm SepSecS. LdSepSecS was found to exist as a tetramer. Leishmania SepSecS enzyme was found to be active and able to complement the ⌬selA deletion in Escherichia coli JS1 strain only in the presence of archaeal PSTK, indicating the conserved nature of the PSTK-SepSecS pathway. LdSepSecS was found to localize in the cytoplasm of the parasite. Gene deletion studies indicate that Leishmania SepSecS is dispensable for the parasite survival. The parasite was found to encode three selenoproteins, which were only expressed in the presence of SepSecS. Selenoproteins of L. donovani are not required for the growth of the promastigotes. Auranofin, a known inhibitor of selenoprotein synthesis showed the same sensitivity toward the wild-type and null mutants suggesting its effect is not through binding to selenoproteins. The three-dimensional structural comparison indicates that human and Leishmania homologs are structurally highly similar but their association modes leading to tetramerization seem different.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Leishmania donovani Encodes a Functional Selenocysteinyl-tRNA Synthase

Manhas¹,

Gowri²,

Madhubala

2016

Journal of Biological Chemistry

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“…They include distant homologs of mammalian SelK and SelT and a selenoprotein, termed SelTryp, that is specific for the kinetoplastid line (15). Moreover, in silico screens by several groups have identified Tb-tRNA Sec , Tb-SerRS, Tb-PSTK, TbSepSecS, Tb-SPS2, and Tb-EFSec, the trypanosomal orthologues of essentially all major components of the Sec-inserting system (16). However, of these only Tb-SerRS, Tb-tRNA Sec (16)(17)(18), and Tb-SPS2 (19) have been subject to preliminary experimental analyses.…”

Section: T Brucei Components Involved In Selenoprotein Formationmentioning

confidence: 99%

The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes

Aeby

Palioura²,

Pusnik

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Selenoenzymes and Selenium Trafficking: An Emerging Target for Therapeutics

Self

Rosario

2004

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Selenoproteins exist within all three domains of life. It is estimated that one‐third of prokaryotes utilize selenium for specific biological purposes, whereas the majority of microorganisms do not use or need selenium. Selenoproteins are unique proteins in which selenocysteine is inserted into the polypeptide chain by highly specialized translational machinery. Alternatively, some selenoproteins in which selenium is incorporated as a labile cofactor have been characterized, and this class of selenoproteins also contains either molybdenum or tungsten. Although several selenoproteins have been well characterized for several decades, the biological functions of these proteins are still being defined. The role of selenoproteins, particularly in human pathogens, has received little attention, yet there is evidence that targeting such proteins could play a major role in drug development. In addition, emerging evidence suggests that many well‐known cancer drugs target a specific class of selenoproteins in mammals, lending credence to the notion that selenoproteins may indeed already be substantial drug targets in the clinic.

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Identification of Leishmania selenoproteins and SECIS element

Cited by 40 publications

References 22 publications

Leishmania donovani Encodes a Functional Selenocysteinyl-tRNA Synthase

Leishmania donovani Encodes a Functional Selenocysteinyl-tRNA Synthase

The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes

Selenoenzymes and Selenium Trafficking: An Emerging Target for Therapeutics

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