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O-phosphoseryl-tRNA(Sec) kinase (PSTK) is an enzyme essential for the biosynthesis of selenocysteine, the 21st natural amino acid incorporated into proteins in both archaea and eukaryotes[1][2]. PSTK specifically recognizes and phosphorylates seryl-tRNA(Sec), converting it to O-phosphoseryl-tRNA(Sec), which is the immediate precursor required for the insertion of selenocysteine into proteins[1][2]. This highly specific and evolutionarily conserved kinase operates in a tRNA-dependent fashion and is a member of the P-loop kinase superfamily, structurally related to gluconate kinase and adenylate kinase[1]. PSTK functions as a homodimer, forming a deep, positively charged groove that accommodates the acceptor stem of tRNA(Sec)[1]. The enzyme uses ATP (requiring divalent metal ions, primarily Mg2+) as a phosphate donor[2]. PSTK ensures the fidelity of selenocysteine decoding by selectively interacting with its cognate tRNA and so plays a critical role in selenoprotein biosynthesis in organisms employing this pathway[1][2]. As of the latest research, there are no known drugs that target PSTK, nor are there established roles for PSTK in human disease or use as a clinical biomarker; its main recognized function is in the translation of selenoproteins[1][2].
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