New Developments in Selenium Biochemistry: Selenocysteine Biosynthesis in Eukaryotes and Archaea |
| |
Authors: | Xue-Ming Xu Bradley A Carlson Yan Zhang Heiko Mix Gregory V Kryukov Richard S Glass Marla J Berry Vadim N Gladyshev Dolph L Hatfield |
| |
Institution: | (1) Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA;(2) Department of Biochemistry, University of Nebraska, Lincoln, NE 68588, USA;(3) Department of Chemistry, The University of Arizona, Tucson, AZ 85721, USA;(4) Department of Cell and Molecular Biology, University of Hawaii at Manoa, Honolulu, HI 96813, USA |
| |
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-tRNASer]Sec to form O-phosphoseryl-tRNASer]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-tRNASer]Sec, and selenophosphate as substrates to generate selenocysteyl-tRNASer]Sec. Sec could be synthesized on tRNASer]Sec from selenide, adenosine triphosphate (ATP), and serine using tRNASer]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.
X.-M. Xu and B. A. Carlson contributed equally to the studies described herein. |
| |
Keywords: | Selenocysteine Selenocysteine biosynthesis Selenocysteine synthase Selenophosphate synthetase Selenoproteins |
本文献已被 PubMed SpringerLink 等数据库收录! |
|