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Exploitation of binding energy for catalysis and design

Author

Listed:
  • Summer B. Thyme

    (Department of Biochemistry,
    Graduate Program in Biomolecular Structure and Design,)

  • Jordan Jarjour

    (Department of Immunology,
    Seattle Children’s Hospital Research Institute, 1900 9th Ave M/S C9S-7, Seattle, Washington 98177, USA)

  • Ryo Takeuchi

    (Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, Seattle, Washington 98109, USA)

  • James J. Havranek

    (Campus Box 8232, Washington University School of Medicine, 4566 Scott Avenue, St Louis, Missouri 63110, USA)

  • Justin Ashworth

    (Department of Biochemistry,
    Graduate Program in Biomolecular Structure and Design,)

  • Andrew M. Scharenberg

    (Department of Immunology,
    Seattle Children’s Hospital Research Institute, 1900 9th Ave M/S C9S-7, Seattle, Washington 98177, USA)

  • Barry L. Stoddard

    (Graduate Program in Biomolecular Structure and Design,
    Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, Seattle, Washington 98109, USA)

  • David Baker

    (Department of Biochemistry,
    Graduate Program in Biomolecular Structure and Design,
    Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA)

Abstract

Enzyme catalysis: asymmetry in endonucleases Enzymes use substrate-binding energy to promote ground-state association and to selectively lower the energy of the reaction transition state. Thyme et al. have determined that for the monomeric homing endonuclease I-AniI, which cleaves double-stranded DNA with high sequence specificity, mutation in the N-terminal domain of the enzyme is responsible for increasing certain kinetic parameters (KD and KM), whereas mutation in the C-terminal domain decreases another kinetic parameter (kcat). This unexpected asymmetry in the utilization of enzyme–substrate binding energy for catalysis may enable researchers to more effectively re-engineer endonucleases to cleave genomic target sites for gene therapy and other biomedical applications.

Suggested Citation

  • Summer B. Thyme & Jordan Jarjour & Ryo Takeuchi & James J. Havranek & Justin Ashworth & Andrew M. Scharenberg & Barry L. Stoddard & David Baker, 2009. "Exploitation of binding energy for catalysis and design," Nature, Nature, vol. 461(7268), pages 1300-1304, October.
    • Handle: RePEc:nat:nature:v:461:y:2009:i:7268:d:10.1038_nature08508
    DOI: 10.1038/nature08508
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    Cited by:

    1. Sarel J Fleishman & Andrew Leaver-Fay & Jacob E Corn & Eva-Maria Strauch & Sagar D Khare & Nobuyasu Koga & Justin Ashworth & Paul Murphy & Florian Richter & Gordon Lemmon & Jens Meiler & David Baker, 2011. "RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite," PLOS ONE, Public Library of Science, vol. 6(6), pages 1-10, June.

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