Abstract
The only well-understood mechanism of zymogen activation is that of the serine proteinases, in which proteolytic cleavage leads to conformational changes resulting in a functional active site. A different mechanism is now unveiled by the crystal structure of pepsinogen. Salt bridges that stabilize the positioning of the N-terminal proenzyme segment across the active site of pepsin are disrupted at low pH, releasing the amino-terminal segment and thereby exposing the catalytic apparatus and the substrate-binding sites.
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James, M., Sielecki, A. Molecular structure of an aspartic proteinase zymogen, porcine pepsinogen, at 1.8 Å resolution. Nature 319, 33–38 (1986). https://doi.org/10.1038/319033a0
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DOI: https://doi.org/10.1038/319033a0
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