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

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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

12 Issues per year

IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

See all formats and pricing
More options …
Volume 383, Issue 7-8 (Aug 2002)


Novel Secretory Vesicle Serpins, Endopin 1 and Endopin 2: Endogenous Protease Inhibitors with Distinct Target Protease Specificities

V. Y. H. Hook / S.-R. Hwang
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2002.115


Secretory vesicles of neuroendocrine cells possess multiple proteases for proteolytic processing of proteins into biologically active peptide components, such as peptide hormones and neurotransmitters. The importance of proteases within secretory vesicles predicts the presence of endogenous protease inhibitors in this subcellular compartment. Notably, serpins represent a diverse class of endogenous protease inhibitors that possess selective target protease specificities, defined by the reactive site loop domains (RSL). In the search for endogenous serpins in model secretory vesicles of neuroendocrine chromaffin cells, the presence of serpins related to α1-antichymotrypsin (ACT) was detected by Western blots with antiACT. Molecular cloning revealed the primary structures of two unique serpins, endopin 1 and endopin 2, that possess homology to ACT. Of particular interest was the observation that distinct RSL domains of these new serpins predicted that endopin 1 would inhibit trypsinlike serine proteases cleaving at basic residues, and endopin 2 would inhibit both elastase and papain that represent serine and cysteine proteases, respectively. Endopin 1 showed selective inhibition of trypsin, but did not inhibit chymotrypsin, elastase, or subtilisin. Endopin 2 demonstrated crossclass inhibition of the cysteine protease papain and the serine protease elastase. Endopin 2 did not inhibit chymotrypsin, trypsin, plasmin, thrombin, furin, or cathepsin B. Endopin 1 and endopin 2 each formed SDSstable complexes with target proteases, a characteristic property of serpins. In neuroendocrine chromaffin cells from adrenal medulla, endopin 1 and endopin 2 were both localized to secretory vesicles. Moreover, the inhibitory activity of endopin 2 was optimized under reducing conditions, which required reduced Cys-374; this property is consistent with the presence of endogenous reducing agents in secretory vesicles in vivo. These new findings demonstrate the presence of unique secretory vesicle serpins, endopin 1 and endopin 2, which possess distinct target protease selectivities. Endopin 1 inhibits trypsinlike proteases; endopin 2 possesses crossclass inhibition for inhibition of papainlike cysteine proteases and elastaselike serine proteases. It will be of interest in future studies to define the endogenous protease targets of these two novel secretory vesicle serpins.

About the article

Published Online: 2005-06-01

Published in Print: 2002-08-27

Citation Information: Biological Chemistry, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2002.115.

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.

J.J. Bond, A. Pernthaner, K. Zhang, S.M. Rosanowski, S. Clerens, S.A. Bisset, I.A.S. Sutherland, J.P. Koolaard, and W.R. Hein
Journal of Proteomics, 2014, Volume 109, Page 356
Zhen Xiao, Josip Blonder, Ming Zhou, and Timothy D. Veenstra
Journal of Proteomics, 2009, Volume 72, Number 1, Page 34
C. Xia, H.Y. Zhang, L. Wu, C. Xu, J.S. Zheng, Y.J. Yan, L.J. Yang, and S. Shu
Research in Veterinary Science, 2012, Volume 93, Number 2, Page 857
Guida M. Portela-Gomes, Lars Grimelius, Erik Wilander, and Mats Stridsberg
Regulatory Peptides, 2010, Volume 165, Number 1, Page 12
Ardalan Minokadeh, Lydiane Funkelstein, Thomas Toneff, Shin-Rong Hwang, Margery Beinfeld, Thomas Reinheckel, Christoph Peters, James Zadina, and Vivian Hook
Molecular and Cellular Neuroscience, 2010, Volume 43, Number 1, Page 98
Vivian Hook, Lydiane Funkelstein, Douglas Lu, Steven Bark, Jill Wegrzyn, and Shin-Rong Hwang
Annual Review of Pharmacology and Toxicology, 2008, Volume 48, Number 1, Page 393
Sallyann L. O'Brien, Ailís Fagan, Edward J.P. Fox, Robert C. Millikan, Aedín C. Culhane, Donal J. Brennan, Amanda H. McCann, Shauna Hegarty, Siobhan Moyna, Michael J. Duffy, Desmond G. Higgins, Karin Jirström, Göran Landberg, and William M. Gallagher
International Journal of Cancer, 2007, Volume 120, Number 7, Page 1434

Comments (0)

Please log in or register to comment.
Log in