Domain structure of bi-functional selenoprotein P.
Human selenoprotein P (SeP), a selenium-rich plasma glycoprotein, is presumed to contain ten selenocysteine residues; one of which is located at the 40th residue in the N-terminal region and the remaining nine localized in the C-terminal third part. We have shown that SeP not only catalyses the reduction of phosphatidylcholine hydroperoxide by glutathione [Saito, Hayashi, Tanaka, Watanabe, Suzuki, Saito and Takahashi (1999) J. Biol. Chem. 274, 2866-2871], but also supplies its selenium to proliferating cells [Saito and Takahashi (2002) Eur. J. Biochem. 269, 5746-5751]. Treatment of SeP with plasma kallikrein resulted in a sequential limited proteolysis (Arg-235-Gln-236 and Arg-242-Asp-243). The N-terminal (residues 1-235) and C-terminal (residues 243-361) fragments exhibited enzyme activity and selenium-supply activity respectively. These results confirm that SeP is a bi-functional protein and suggest that the first selenocysteine residue is the active site of the enzyme and the remaining nine residues function as a selenium supplier.
Saito
Yoshiro
Y
Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Sato
Noriko
N
Hirashima
Masaki
M
Takebe
Gen
G
Nagasawa
Shigeharu
S
Takahashi
Kazuhiko
K
D001665:Binding Sites; D001777:Blood Coagulation / Q000502:physiology; D045744:Cell Line, Tumor; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D019169:Jurkat Cells / Q000201:enzymology / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D020842:Plasma Kallikrein / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012643:Selenium / Q000378:metabolism; D051149:Selenoprotein P; D051140:Selenoproteins; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D020842:Plasma Kallikrein; D012643:Selenium