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Rare skeletal condition caused by enzyme’s failure to rescue a catalytic cycle

When enzymes require rescue strategies to complete progression through their reaction, but natural safety nets fail, disease states can ensue.
By
  1. Karen N. Allen

    1. Karen N. Allen is in the Department of Chemistry, Boston University, Boston, Massachusetts 02215, USA.

Enzymes are the workhorses of the cell, enabling metabolic reactions to occur efficiently on timescales compatible with life. Known for their fidelity and catalytic prowess, enzymes allow reaction cycles with specific substrates to occur repeatedly without error. But what happens when an enzyme’s catalytic cycle breaks down? Or, worse, when the natural mechanism for recovering from such a failure also breaks down? Writing in Nature, Jacobs et al.1 trace the root cause of a hereditary skeletal condition, known as Catel–Manzke syndrome, to a defect in the function of a ‘rescue’ enzyme, uncovering the weakness in the catalytic cycle that it was meant to protect.

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Nature 646, 45-46 (2025)

doi: https://doi.org/10.1038/d41586-025-02428-7

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Competing Interests

The author declares no competing interests.

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