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Catalysis by Enzyme Conformational Change

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Book cover Orotidine Monophosphate Decarboxylase

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 238))

Abstract

An energy decomposition scheme is presented to elucidate the importance of the change of protein conformation substates to the reduction of activation barrier in an enzyme-catalyzed reaction. The analysis is illustrated by the reaction of orotidine 5′-monophosphate decarboxylase (ODCase), in which the catalyzed reaction is at least 1017 faster than the spontaneous reaction. Analysis reveals that the enzyme conformation is more distorted in the reactant state than in the transition state. The energy released from conformational relaxation of the protein is the main source of the rate enhancement. The proposed mechanism is consistent with results from site-directed mutagenesis where mutations remote from the reaction center affect k cat but not K M.

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Abbreviations

AMI :

Austin Model 1

EVB :

Empirical valence bond

FEP :

Free energy perturbation

MM :

Molecular mechanics

ODCase :

Orotidine 5′-monophosphate decarboxylase

OMP :

Orotidine 5′-monophosphate

PMF :

Potential of mean force

QM :

Quantum mechanics

QM/MM :

Combined quantum mechanical and molecular mechanical

TS :

Transition state

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Acknowledgements

We thank the NIH for support for the research at the University of Minnesota. RK thanks NSERC Canada for support through a Discovery Grant.

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Authors and Affiliations

  1. Department of Chemistry, Supercomputing Institute, and Digital Technology Center, University of Minnesota, Minneapolis, MN , 55455, USA

    Jiali Gao

  2. Computational Science, Korea Institute for Advanced Study, 130-722, Seoul, Korea

    Kyoungrim Lee Byun

  3. Department of Chemistry, University of Toronto, Toronto, Ontario, M5S 3H6, Canada

    Ronald Kluger

Authors
  1. Jiali Gao
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  2. Kyoungrim Lee Byun
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  3. Ronald Kluger
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Corresponding author

Correspondence to Jiali Gao .

Editor information

J.K. Lee

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Gao, J., Byun, K.L., Kluger, R. Catalysis by Enzyme Conformational Change. In: Lee, J. (eds) Orotidine Monophosphate Decarboxylase. Topics in Current Chemistry, vol 238. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b94541

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  • DOI: https://doi.org/10.1007/b94541

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-20566-1

  • Online ISBN: 978-3-540-40039-4

  • eBook Packages: Springer Book Archive

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