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Pyrrolysyl-tRNA synthetase–tRNAPyl structure reveals the molecular basis of orthogonality

Kayo Nozawa, Patrick O’Donoghue, Sarath Gundllapalli, Yuhei Araiso, Ryuichiro Ishitani, Takuya Umehara, Dieter Söll () and Osamu Nureki ()
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Kayo Nozawa: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B34 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan
Patrick O’Donoghue: Department of Molecular Biophysics and Biochemistry,
Sarath Gundllapalli: Department of Molecular Biophysics and Biochemistry,
Yuhei Araiso: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B34 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan
Ryuichiro Ishitani: Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Takuya Umehara: Department of Molecular Biophysics and Biochemistry,
Dieter Söll: Department of Molecular Biophysics and Biochemistry,
Osamu Nureki: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B34 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan

Nature, 2009, vol. 457, issue 7233, 1163-1167

Abstract: Pyrrolysine's route into proteins Pyrrolysine is known as the 22nd 'natural' amino acid, complementing the 20 standard or proteinogenic amino acids and selenocysteine. Although pyrrolysine appears rarely in proteins, the machinery to utilize it has existed since the time of the last universal common ancestor. It is inserted in proteins by a specific suppressor tRNA that recognizes the UAG stop codon. This pyrrolysine-specific tRNA, tRNAPyl, is charged by the tRNA synthetase PylRS. This work reports the determination of the structure of the orthogonal Desulfitobacterium hafniense tRNAPyl–PylRS pair, revealing the molecular basis of the orthogonality both in vivo and in vitro. The structure of the co-complex reveals the distinct interactions of the protein and tRNA that distinguish this pair from those which function with the 20 standard amino acids.

Date: 2009
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DOI: 10.1038/nature07611

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