Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 382, Issue 5

Issues

Cathepsins X and B Display Distinct Activity Profiles That Can Be Exploited for Inhibitor Design

R. Ménard / C. Therrien / P. Lachance / T. Sulea / H. Qi / A. Alvarez-Hernandez / W.R. Roush .
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2001.102

Abstract

The carboxypeptidase and endopeptidase activities of cathepsins X and B, as well as their inhibition by E 64 derivatives, have been investigated in detail and compared. The results clearly demonstrate that cathepsins X and B do not share similar activity profiles against substrates and inhibitors. Using quenched fluorogenic substrates, we show that cathepsin X preferentially cleaves substrates through a monopeptidyl carboxypeptidase pathway, while cathepsin B displays a preference for the dipeptidyl pathway. The preference for one or the other pathway is about the same for both enzymes, i. e. approximately 2 orders of magnitude. Cleavage of a Cterminal dipeptide of a substrate by cathepsin X can be observed under conditions that preclude efficient monopeptidyl carboxypeptidase activity. In addition, an inhibitor designed to exploit the unique structural features responsible for the carboxypeptidase activity of cathepsin X has been synthesized and tested against cathepsins X, B and L. Although of moderate potency, this E-64 derivative is the first reported example of a cathepsin Xspecific inhibitor. By comparison, CA074 was found to inactivate cathepsin B at least 34000-fold more efficiently than cathepsin X.

About the article

Published Online: 2005-06-01

Published in Print: 2001-05-05


Citation Information: Biological Chemistry, Volume 382, Issue 5, Pages 839–845, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2001.102.

Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Janko Kos, Andreja Sekirnik, Aleš Premzl, Valentina Zavašnik Bergant, Tomaž Langerholc, Urška Repnik, Boris Turk, Bernd Werle, Rastko Golouh, Matjaž Jeras, and Vito Turk
Experimental Cell Research, 2005, Volume 306, Number 1, Page 103
[2]
Nataša Obermajer, Aleš Premzl, Tina Zavašnik Bergant, Boris Turk, and Janko Kos
Experimental Cell Research, 2006, Volume 312, Number 13, Page 2515
[3]
Alejandro Alvarez Hernandez and William R Roush
Current Opinion in Chemical Biology, 2002, Volume 6, Number 4, Page 459
[4]
L. Sevenich, U. Schurigt, K. Sachse, M. Gajda, F. Werner, S. Muller, O. Vasiljeva, A. Schwinde, N. Klemm, J. Deussing, C. Peters, and T. Reinheckel
Proceedings of the National Academy of Sciences, 2010, Volume 107, Number 6, Page 2497

Comments (0)

Please log in or register to comment.
Log in