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An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA

Author

Listed:
  • T. Martin Schmeing

    (Department of Molecular Biophysics and Biochemistry)

  • Kevin S. Huang

    (Department of Molecular Biophysics and Biochemistry)

  • Scott A. Strobel

    (Department of Molecular Biophysics and Biochemistry
    Yale University)

  • Thomas A. Steitz

    (Department of Molecular Biophysics and Biochemistry
    Yale University
    Howard Hughes Medical Institute)

Abstract

Don't go near the water Many kinds of enzymes need to protect their substrates from unwanted hydrolysis. Koshland proposed more than 40 years ago that these enzymes — he was looking specifically at hexokinase — adopt the catalytically competent conformation only when the appropriate substrates are bound and produce an ‘induced fit’ conformational change. Later work showed that it is indeed ‘induced fit’ that stops hexokinase from hydrolysing ATP when there is no glucose about. Structural studies of the large ribosomal subunit now show that a similar fit mechanism operates here too. This provides the answer to the long-standing question of how the nascent peptide in the P site of the ribosome avoids hydrolysis by peptidyl tRNA until the termination step of protein synthesis. This mechanism may well have been available to the ribozymes in an RNA world before proteins came on the scene.

Suggested Citation

  • T. Martin Schmeing & Kevin S. Huang & Scott A. Strobel & Thomas A. Steitz, 2005. "An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA," Nature, Nature, vol. 438(7067), pages 520-524, November.
  • Handle: RePEc:nat:nature:v:438:y:2005:i:7067:d:10.1038_nature04152
    DOI: 10.1038/nature04152
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    Cited by:

    1. Victor E. Cruz & Christine S. Weirich & Nagesh Peddada & Jan P. Erzberger, 2024. "The DEAD-box ATPase Dbp10/DDX54 initiates peptidyl transferase center formation during 60S ribosome biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Corentin R. Fostier & Farès Ousalem & Elodie C. Leroy & Saravuth Ngo & Heddy Soufari & C. Axel Innis & Yaser Hashem & Grégory Boël, 2023. "Regulation of the macrolide resistance ABC-F translation factor MsrD," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Martino Morici & Sara Gabrielli & Keigo Fujiwara & Helge Paternoga & Bertrand Beckert & Lars V. Bock & Shinobu Chiba & Daniel N. Wilson, 2024. "RAPP-containing arrest peptides induce translational stalling by short circuiting the ribosomal peptidyltransferase activity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Thu Giang Nguyen & Christina Ritter & Eva Kummer, 2023. "Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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