Biochimica et Biophysica Acta 2014-06-01

Pyrrolysyl-tRNA synthetase: an ordinary enzyme but an outstanding genetic code expansion tool.

Wei Wan, Jeffery M Tharp, Wenshe R Liu

Index: Biochim. Biophys. Acta 1844(6) , 1059-70, (2014)

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Abstract

The genetic incorporation of the 22nd proteinogenic amino acid, pyrrolysine (Pyl) at amber codon is achieved by the action of pyrrolysyl-tRNA synthetase (PylRS) together with its cognate tRNA(Pyl). Unlike most aminoacyl-tRNA synthetases, PylRS displays high substrate side chain promiscuity, low selectivity toward its substrate α-amine, and low selectivity toward the anticodon of tRNA(Pyl). These unique but ordinary features of PylRS as an aminoacyl-tRNA synthetase allow the Pyl incorporation machinery to be easily engineered for the genetic incorporation of more than 100 non-canonical amino acids (NCAAs) or α-hydroxy acids into proteins at amber codon and the reassignment of other codons such as ochre UAA, opal UGA, and four-base AGGA codons to code NCAAs. Copyright © 2014 Elsevier B.V. All rights reserved.