Literature summary for 2.9.1.2 extracted from

Palioura, S.; Sherrer, R.L.; Steitz, T.A.; S�ll, D.; Simonovic, M.
The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation (2009), Science, 325, 321-325.

Search for more literature for 2.9.1.2

Crystallization (Commentary)

Crystallization (Comment)	Organism
crystal structure of the quaternary complex between human SepSecS, unacylated tRNASec, and a mixture of O-phosphoserine and thiophosphate to 2.8 A resolution	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
K173A	in vivo activity of the mutant is indistinguishable from that of the wild-type enzyme	Homo sapiens
K173M	in vivo activity of the mutant is indistinguishable from that of the wild-type enzyme	Homo sapiens
Q105A	mutant is inactive in vivo	Homo sapiens
R313A	mutant is inactive in vivo	Homo sapiens
R75A	mutant is inactive in vivo	Homo sapiens
R97A	in vivo activity of the mutant is indistinguishable from that of the wild-type enzyme	Homo sapiens
R97Q	in vivo activity of the mutant is indistinguishable from that of the wild-type enzyme	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-phosphoseryl-tRNASec + selenophosphate	Homo sapiens	selenocysteine is the only genetically encoded amino acid in humans whose biosynthesis occurs on its cognate transfer RNA (tRNA). O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase catalyzes the final step of selenocysteine formation by a tRNA-dependent mechanism	L-selenocysteinyl-tRNASec + phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9HD40	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
O-phospho-L-seryl-tRNASec + selenophosphate + H2O = L-selenocysteinyl-tRNASec + 2 phosphate	proposed pyridoxal 5'-phosphate mechanism of L-phosphoseryl-tRNA to L-selenocysteinyl-tRNA conversion: the reaction begins by the covalently attached O-phospho-L-serine being brought into the proximity of the Schiff base when L-phosphoseryl-tRNASec binds to the enzyme. The amino group of O-phospho-L-serine can then attack the Schiff base formed between Lys284 and pyridoxal 5'-phosphate, which yields an external aldimine. The reoriented side chain of Lys284 abstracts the Calpha proton from O-phospho-L-serine, and the electron delocalization by the pyridine ring assists in rapid beta-elimination of the phosphate group, which produces an intermediate dehydroalanyl-tRNASec. After phosphate dissociation and binding of selenophosphate, the concomitant attack of water on the selenophosphate group and of the nucleophilic selenium onto the highly reactive dehydroalanyl moiety yield an oxidized form of L-phosphoseryl-tRNASec. The protonated Lys284, returns the proton to the Calpha carbon and then attacks pyridoxal 5'-phosphate to form an internal aldimine. Finally, Sec-tRNASec is released from the active site	Homo sapiens	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-phosphoseryl-tRNASec + selenophosphate	selenocysteine is the only genetically encoded amino acid in humans whose biosynthesis occurs on its cognate transfer RNA (tRNA). O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase catalyzes the final step of selenocysteine formation by a tRNA-dependent mechanism	Homo sapiens	L-selenocysteinyl-tRNASec + phosphate	-	?
O-phospho-L-seryl-tRNASec + selenophosphate	proposed pyridoxal 5'-phosphate mechanism of L-phosphoseryl-tRNA to L-selenocysteinyl-tRNA conversion: the reaction begins by the covalently attached O-phospho-L-serine being brought into the proximity of the Schiff base when L-phosphoseryl-tRNASec binds to the enzyme. The amino group of O-phospho-L-serine can then attack the Schiff base formed between Lys284 and pyridoxal 5'-phosphate, which yields an external aldimine. The reoriented side chain of Lys284 abstracts the Calpha proton from O-phospho-L-serine, and the electron delocalization by the pyridine ring assists in rapid beta-elimination of the phosphate group, which produces an intermediate dehydroalanyl-tRNASec. After phosphate dissociation and binding of selenophosphate, the concomitant attack of water on the selenophosphate group and of the nucleophilic selenium onto the highly reactive dehydroalanyl moiety yield an oxidized form of L-phosphoseryl-tRNASec. The protonated Lys284, returns the proton to the Calpha carbon and then attacks pyridoxal 5'-phosphate to form an internal aldimine. Finally, Sec-tRNASec is released from the active site	Homo sapiens	L-selenocysteinyl-tRNASec + phosphate	-	?

Subunits

Subunits	Comment	Organism
tetramer	two SepSecS monomers form a homodimer, and two active sites are formed at the dimer interface. The two homodimers associate into a tetramer through interactions between the N-terminal alpha1-loop-alpha2 motifs	Homo sapiens

Synonyms

Synonyms	Comment	Organism
O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase	-	Homo sapiens
SepSecS	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
pyridoxal 5'-phosphate	pyridoxal 5'-phosphatedependent mechanism of Sec-tRNASec formation. Each SepSecS monomer has a pyridoxal 5'-phosphate cofactor covalently linked to the Nepsilon-amino group of the conserved Lys284 by means of formation of a Schiff base	Homo sapiens

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Release 2023.1 (January 2023)