Protein-based peptide-bond formation by aminoacyl-tRNA protein transferase

Kazunori Watanabe, Yukimatsu Toh, Kyoko Suto, Yoshihiro Shimizu, Natsuhisa Oka, Takeshi Wada, Kozo Tomita

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Eubacterial leucyl/phenylalanyl-tRNA protein transferase (LF-transferase) catalyses peptide-bond formation by using Leu-tRNALeu (or Phe-tRNAPhe) and an amino-terminal Arg (or Lys) of a protein, as donor and acceptor substrates, respectively. However, the catalytic mechanism of peptide-bond formation by LF-transferase remained obscure. Here we determine the structures of complexes of LF-transferase and phenylalanyl adenosine, with and without a short peptide bearing an N-terminal Arg. Combining the two separate structures into one structure as well as mutation studies reveal the mechanism for peptide-bond formation by LF-transferase. The electron relay from Asp 186 to Gln 188 helps Gln 188 to attract a proton from the α-amino group of the N-terminal Arg of the acceptor peptide. This generates the attacking nucleophile for the carbonyl carbon of the aminoacyl bond of the aminoacyl-tRNA, thus facilitating peptide-bond formation. The protein-based mechanism for peptide-bond formation by LF-transferase is similar to the reverse reaction of the acylation step observed in the peptide hydrolysis reaction by serine proteases.

Original languageEnglish
Pages (from-to)867-871
Number of pages5
JournalNature
Volume449
Issue number7164
DOIs
Publication statusPublished - Oct 18 2007
Externally publishedYes

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Transferases
Transfer RNA
Peptides
Proteins
leucyltransferase
RNA, Transfer, Leu
RNA, Transfer, Phe
Acylation
Serine Proteases
Adenosine
Protons
Hydrolysis
Carbon
Electrons
Mutation

ASJC Scopus subject areas

  • General

Cite this

Watanabe, K., Toh, Y., Suto, K., Shimizu, Y., Oka, N., Wada, T., & Tomita, K. (2007). Protein-based peptide-bond formation by aminoacyl-tRNA protein transferase. Nature, 449(7164), 867-871. https://doi.org/10.1038/nature06167

Protein-based peptide-bond formation by aminoacyl-tRNA protein transferase. / Watanabe, Kazunori; Toh, Yukimatsu; Suto, Kyoko; Shimizu, Yoshihiro; Oka, Natsuhisa; Wada, Takeshi; Tomita, Kozo.

In: Nature, Vol. 449, No. 7164, 18.10.2007, p. 867-871.

Research output: Contribution to journalArticle

Watanabe, K, Toh, Y, Suto, K, Shimizu, Y, Oka, N, Wada, T & Tomita, K 2007, 'Protein-based peptide-bond formation by aminoacyl-tRNA protein transferase', Nature, vol. 449, no. 7164, pp. 867-871. https://doi.org/10.1038/nature06167
Watanabe K, Toh Y, Suto K, Shimizu Y, Oka N, Wada T et al. Protein-based peptide-bond formation by aminoacyl-tRNA protein transferase. Nature. 2007 Oct 18;449(7164):867-871. https://doi.org/10.1038/nature06167
Watanabe, Kazunori ; Toh, Yukimatsu ; Suto, Kyoko ; Shimizu, Yoshihiro ; Oka, Natsuhisa ; Wada, Takeshi ; Tomita, Kozo. / Protein-based peptide-bond formation by aminoacyl-tRNA protein transferase. In: Nature. 2007 ; Vol. 449, No. 7164. pp. 867-871.
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