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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Selectivity of propeptide-enzyme interaction in cathepsin L-like cysteine proteases

Klaus Schilling1 / Alexandra Körner2 / Saskia Sehmisch3 / Annett Kreusch4 / Ramona Kleint5 / Yvonne Benedix6 / Anne Schlabrakowski7 / Bernd Wiederanders8

1Institut für Biochemie I, Universitätsklinikum Jena, Nonnenplan 2, D-07743 Jena, Germany

2Institut für Biochemie I, Universitätsklinikum Jena, Nonnenplan 2, D-07743 Jena, Germany

3Institut für Biochemie I, Universitätsklinikum Jena, Nonnenplan 2, D-07743 Jena, Germany

4Institut für Biochemie I, Universitätsklinikum Jena, Nonnenplan 2, D-07743 Jena, Germany

5Institut für Biochemie I, Universitätsklinikum Jena, Nonnenplan 2, D-07743 Jena, Germany

6Institut für Biochemie I, Universitätsklinikum Jena, Nonnenplan 2, D-07743 Jena, Germany

Present address: Pathologisches Institut der Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstr. 12, D-91054 Erlangen, Germany.
7Institut für Biochemie I, Universitätsklinikum Jena, Nonnenplan 2, D-07743 Jena, Germany

8Institut für Biochemie I, Universitätsklinikum Jena, Nonnenplan 2, D-07743 Jena, Germany

Corresponding author

Citation Information: Biological Chemistry. Volume 390, Issue 2, Pages 167–174, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2009.023, November 2008

Publication History

Received:
2008-09-02
Accepted:
2008-11-13
Published Online:
2008-11-29

Abstract

Cathepsin L-like endopeptidases of the papain family are synthesized as proenzymes. N-terminal proregions are essential for folding and latency of the enzyme unit. While selectivity has been reported for the inhibitory function of papain-family propeptides, there is no systematic investigation of the selectivity of their chaperone-like function to date. The chaperone-like cross-reactivity between the cathepsins S, K, and L were thoroughly quantified in trans-experiments, i.e., with isolated propeptides and mature enzymes, and compared to the inhibitory cross-reactivity. The three endopeptidases have been chosen due to only minimal evolutionary distance and nearly identical X-ray structures of their zymogenes. The intramolecular chaperone function of the proregion was found to be more selective than the inhibitory activity and significant differences were found between the selectivity profiles, underlining the assumption that the inhibitory and the chaperone-like propeptide functions are autonomous. Considering the data published on the intramolecular chaperone-like propeptide function within other protease classes as well, our data suggest that intrinsically structured propeptides are more selective than intrinsically unstructured propeptides, i.e., those adopting tertiary structure elements only in complex with their maternal enzyme.

Keywords: cathepsin L-like endopeptidases; inhibition; intramolecular chaperone; proregion; refolding

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