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Biochemistry

Molecular cloaking devices

Nature volume 453, pages 861–862 (2008)Cite this article

Protease enzymes cut other proteins into pieces, but some can be blocked by inhibitors. One such inhibitor binds to the substrate rather than the enzyme, suggesting a new tactic for drug discovery.

Most drug developers try to identify small molecules that bind to a target enzyme with high affinity and specificity. Binding usually occurs at the enzyme's active site; by nestling into this molecular pocket, the drug blocks binding of the enzyme's natural substrate. Alternatively, the drug binds to the enzyme at a location that is distinct from the active site, thus locking the enzyme into a conformation that either strongly inhibits or activates substrate processing in the active site itself. These two models of binding explain the behaviour of most drugs.

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Figure 1: Targets for enzyme inhibition.

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Authors and Affiliations

  1. Thomas Kodadek is in the Departments of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9185, USA. e-mail: thomas.kodadek@utsouthwestern.edu,

    Thomas Kodadek

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  1. Thomas Kodadek
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Kodadek, T. Molecular cloaking devices. Nature 453, 861–862 (2008). https://doi.org/10.1038/453861a

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