Nature 319, 33 - 38 (02 January 1986); doi:10.1038/319033a0

Molecular structure of an aspartic proteinase zymogen, porcine pepsinogen, at 1.8 Å resolution

Michael N. G. James & Anita R. Sielecki

Medical Research Council of Canada Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7

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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