title: New developments in selenium biochemistry: selenocysteine biosynthesis in eukaryotes and archaea.
abstract: We used comparative genomics and experimental analyses to show that (1) eukaryotes and archaea, which possess the selenocysteine (Sec) protein insertion machinery contain an enzyme, O-phosphoseryl-transfer RNA (tRNA) [Ser]Sec kinase (designated PSTK), which phosphorylates seryl-tRNA [Ser]Sec to form O-phosphoseryl-tRNA [Ser]Sec and (2) the Sec synthase (SecS) in mammals is a pyridoxal phosphate-containing protein previously described as the soluble liver antigen (SLA). SecS uses the product of PSTK, O-phosphoseryl-tRNA[Ser]Sec, and selenophosphate as substrates to generate selenocysteyl-tRNA [Ser]Sec. Sec could be synthesized on tRNA [Ser]Sec from selenide, adenosine triphosphate (ATP), and serine using tRNA[Ser]Sec, seryl-tRNA synthetase, PSTK, selenophosphate synthetase, and SecS. The enzyme that synthesizes monoselenophosphate is a previously identified selenoprotein, selenophosphate synthetase 2 (SPS2), whereas the previously identified mammalian selenophosphate synthetase 1 did not serve this function. Monoselenophosphate also served directly in the reaction replacing ATP, selenide, and SPS2, demonstrating that this compound was the active selenium donor. Conservation of the overall pathway of Sec biosynthesis suggests that this pathway is also active in other eukaryotes and archaea that contain selenoproteins.
authors.affiliation: Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Xu
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Carlson
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Heiko
authors.initials: H
authors.lastname: Mix
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Kryukov
authors.forename: Richard S
authors.initials: RS
authors.lastname: Glass
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Berry
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
mesh_terms: D000818:Animals; D001105:Archaea / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000378:metabolism; D008954:Models, Biological; D010770:Phosphotransferases / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012643:Selenium / Q000378:metabolism*; D017279:Selenocysteine / Q000096:biosynthesis*; D051140:Selenoproteins / Q000378:metabolism
chemical_list: D012346:RNA, Transfer, Amino Acyl; D051140:Selenoproteins; D017279:Selenocysteine; D010770:Phosphotransferases; C062762:selenophosphate synthetase; D012643:Selenium