2Z67

Crystal structure of archaeal O-phosphoseryl-tRNA(Sec) selenium transferase (SepSecS)

Summary for 2Z67

• Entry DOI: 10.2210/pdb2z67/pdb
• Descriptor: O-phosphoseryl-tRNA(Sec) selenium transferase, PYRIDOXAL-5'-PHOSPHATE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: selenocysteine biosynthesis, seven-stranded bete-strand, pyridoxal-5'-phosphate, protein biosynthesis, pyridoxal phosphate, selenium, transferase
• Biological source: Methanococcus maripaludis
• Total number of polymer chains: 4
• Total formula weight: 205781.10

Authors

Araiso, Y.,Ishitani, R.,Pailouer, S.,Oshikane, H.,Domae, N.,Soll, D.,Nureki, O. (deposition date: 2007-07-23, release date: 2008-04-29, Last modification date: 2025-03-26)

Primary citation

Araiso, Y.,Palioura, S.,Ishitani, R.,Sherrer, R.L.,O'Donoghue, P.,Yuan, J.,Oshikane, H.,Domae, N.,Defranco, J.,Soll, D.,Nureki, O.
Structural insights into RNA-dependent eukaryal and archaeal selenocysteine formation.
Nucleic Acids Res., 36:1187-1199, 2008

PubMed Abstract: The micronutrient selenium is present in proteins as selenocysteine (Sec). In eukaryotes and archaea, Sec is formed in a tRNA-dependent conversion of O-phosphoserine (Sep) by O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS). Here, we present the crystal structure of Methanococcus maripaludis SepSecS complexed with PLP at 2.5 A resolution. SepSecS, a member of the Fold Type I PLP enzyme family, forms an (alpha2)2 homotetramer through its N-terminal extension. The active site lies on the dimer interface with each monomer contributing essential residues. In contrast to other Fold Type I PLP enzymes, Asn247 in SepSecS replaces the conserved Asp in binding the pyridinium nitrogen of PLP. A structural comparison with Escherichia coli selenocysteine lyase allowed construction of a model of Sep binding to the SepSecS catalytic site. Mutations of three conserved active site arginines (Arg72, Arg94, Arg307), protruding from the neighboring subunit, led to loss of in vivo and in vitro activity. The lack of active site cysteines demonstrates that a perselenide is not involved in SepSecS-catalyzed Sec formation; instead, the conserved arginines may facilitate the selenation reaction. Structural phylogeny shows that SepSecS evolved early in the history of PLP enzymes, and indicates that tRNA-dependent Sec formation is a primordial process.

PubMed: 18158303
DOI: 10.1093/nar/gkm1122

Experimental method

X-RAY DIFFRACTION (2.5 Å)