Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 1998 Apr;7(4):815-36.
doi: 10.1002/pro.5560070401.

Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes

A R Khan  1 , M N James
Affiliations
Review

Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes

A R Khan et al. Protein Sci. 1998 Apr.

Abstract

Proteolytic enzymes are synthesized as inactive precursors, or "zymogens," to prevent unwanted protein degradation, and to enable spatial and temporal regulation of proteolytic activity. Upon sorting or appropriate compartmentalization, zymogen conversion to the active enzyme typically involves limited proteolysis and removal of an "activation segment." The sizes of activation segments range from dipeptide units to independently folding domains comprising more than 100 residues. A common form of the activation segment is an N-terminal extension of the mature enzyme, or "prosegment," that sterically blocks the active site, and thereby prevents binding of substrates. In addition to their inhibitory role, prosegments are frequently important for the folding, stability, and/or intracellular sorting of the zymogen. The mechanisms of conversion to active enzymes are diverse in nature, ranging from enzymatic or nonenzymatic cofactors that trigger activation, to a simple change in pH that results in conversion by an autocatalytic mechanism. Recent X-ray crystallographic studies of zymogens and comparisons with their active counterparts have identified the structural changes that accompany conversion. This review will focus upon the structural basis for inhibition by activation segments, as well as the molecular events that lead to the conversion of zymogens to active enzymes.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Biol Chem. 1990 Apr 25;265(12):6949-53 - PubMed
    1. Annu Rev Biophys Biophys Chem. 1990;19:189-215 - PubMed
    1. J Cell Biol. 1990 Aug;111(2):361-8 - PubMed
    1. Biochemistry. 1990 Jun 19;29(24):5783-9 - PubMed
    1. Biochemistry. 1990 Aug 14;29(32):7366-72 - PubMed

Publication types

LinkOut - more resources