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Synthesis

Protein Structure Helps Decipher Route To Selenocysteine

X-ray structure of selenocysteine's transfer RNA coupled to the SepSecS enzyme provides a better view of selenocysteine biosynthesis

by Celia Henry Arnaud
July 20, 2009 | A version of this story appeared in Volume 87, Issue 29

Transformation
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SepSecS makes selenocysteine by converting phosphoseryl-bound tRNA to selenocysteinyl-tRNA.
SepSecS makes selenocysteine by converting phosphoseryl-bound tRNA to selenocysteinyl-tRNA.

Selenocysteine is unique among amino acids in that it doesn’t have its own transfer RNA synthetase enzyme but is instead synthesized directly on its specific tRNA (tRNASec). An enzyme known as SepSecS catalyzes the still poorly understood final step in this process in which a phosphoseryl group is converted to selenocysteinyl using selenophosphate as the selenium donor. Dieter Söll of Yale University; Miljan Simonovi´c of the University of Illinois, Chicago; and coworkers now report a 2.8-Å resolution X-ray crystal structure of human tRNASec complexed with SepSecS, phosphoserine, and thiophosphate that provides a better view on how selenocysteine biosynthesis plays out (Science 2009, 325, 321). With the crystal structure and other data in hand, the researchers propose that the phosphoseryl-to-selenocysteinyl conversion occurs via a pyridoxal phosphate (PLP)-dependent mechanism involving a dehydroalanine intermediate. The lack of an aspartate anion to stabilize the pro­tonated nitrogen atom of PLP’s pyridine ring distinguishes SepSecS from most other PLP enzymes, they note. A subsequent series of reactions involving phosphate and selenophosphate completes the pathway from the intermediate to selenocysteine.

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