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Mandelate racemase and muconate lactonizing enzyme are mechanistically distinct and structurally homologous

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Abstract

MANDELATE racemase (MR) and muconate lactonizing enzyme (MLE) catalyse separate and mechanistically distinct reactions necessary for the catabolism of aromatic acids by Pseudomonas putida1–3. The X-ray crystal structure of MR, solved at 2.5 Å resolution, reveals that the secondary, tertiary and quaternary structures of MR and MLE4 are remarkably similar; also, MR and MLE are about 26% identical in primary structure5. However, MR has no detectable MLE activity and vice versa. Thus, MR and MLE constitute the first example of enzymes that catalyse different reactions, as opposed to mechanistically identical reactions on different substrates, yet possess sufficient structural and sequence identity that they are likely to have evolved from a common ancestor. The discovery that MR and MLE catalyse different reactions but share a common structural framework has broad implications for the natural evolution of enzymes and metabolic pathways, as well as for the rational modification of enzyme activities.

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Author information

Author notes

  1. David J. Neidhart

    Present address: Protein Crystallography Laboratory, D-47E, Abbott Laboratories, Abbott Park, Illinois, 60064, USA

  2. Gregory A. Petsko

    Present address: Rosenstiel Center, Brandeis University, Waltham, Massachusetts, 02254, USA

Authors and Affiliations

  1. Department of Chemistry, Massachussetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    David J. Neidhart & Gregory A. Petsko

  2. Department of Pharmaceutical Chemistry, University of California, San Francisco, California, 94143, USA

    David J. Neidhart & Gregory A. Petsko

  3. Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, 20742, USA

    George L. Kenyon

Authors
  1. David J. Neidhart
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  2. George L. Kenyon
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  3. John A. Gerlt
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  4. Gregory A. Petsko
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Neidhart, D., Kenyon, G., Gerlt, J. et al. Mandelate racemase and muconate lactonizing enzyme are mechanistically distinct and structurally homologous. Nature 347, 692–694 (1990). https://doi.org/10.1038/347692a0

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  • DOI: https://doi.org/10.1038/347692a0

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