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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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Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease

Cynthia Tallant1 / Raquel García-Castellanos2 / Aniebrys Marrero3 / Francesc Canals4 / Yongzheng Yang5 / Jean-Louis Reymond6 / Maria Solà7 / Ulrich Baumann8 / F. Xavier Gomis-Rüth9

1Departament de Biologia Estructural, Institut de Biologia Molecular de Barcelona, C.S.I.C., c/ Jordi Girona, 18-26, E-08034 Barcelona, Spain, and Parc Científic de Barcelona, c/ Josep Samitier, 1-5, E-08028 Barcelona, Spain

2Departament de Biologia Estructural, Institut de Biologia Molecular de Barcelona, C.S.I.C., c/ Jordi Girona, 18-26, E-08034 Barcelona, Spain, and Parc Científic de Barcelona, c/ Josep Samitier, 1-5, E-08028 Barcelona, Spain
First two authors contributed equally to this work.

3Departament de Biologia Estructural, Institut de Biologia Molecular de Barcelona, C.S.I.C., c/ Jordi Girona, 18-26, E-08034 Barcelona, Spain, and Parc Científic de Barcelona, c/ Josep Samitier, 1-5, E-08028 Barcelona, Spain

4Proteomics Laboratory, Medical Oncology Research Program, Vall d'Hebron University Hospital Research Institute, Psg. Vall d'Hebron, 119-129, E-08035 Barcelona, Spain

5Departement für Chemie und Biochemie, Universität Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

6Departement für Chemie und Biochemie, Universität Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

7Departament de Biologia Estructural, Institut de Biologia Molecular de Barcelona, C.S.I.C., c/ Jordi Girona, 18-26, E-08034 Barcelona, Spain, and Parc Científic de Barcelona, c/ Josep Samitier, 1-5, E-08028 Barcelona, Spain

8Departament de Biologia Estructural, Institut de Biologia Molecular de Barcelona, C.S.I.C., c/ Jordi Girona, 18-26, E-08034 Barcelona, Spain, and Parc Científic de Barcelona, c/ Josep Samitier, 1-5, E-08028 Barcelona, Spain and Departement für Chemie und Biochemie, Universität Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

9Departament de Biologia Estructural, Institut de Biologia Molecular de Barcelona, C.S.I.C., c/ Jordi Girona, 18-26, E-08034 Barcelona, Spain, and Parc Científic de Barcelona, c/ Josep Samitier, 1-5, E-08028 Barcelona, Spain

Corresponding authors ;

Citation Information: Biological Chemistry. Volume 388, Issue 11, Pages 1243–1253, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: 10.1515/BC.2007.143, November 2007

Publication History

Received:
2007-05-08
Accepted:
2007-07-12
Published Online:
2007-11-02

Abstract

Human growth and development are conditioned by insulin-like growth factors (IGFs), which have also implications in pathology. Most IGF molecules are sequestered by IGF-binding proteins (IGFBPs) so that exertion of IGF activity requires disturbance of these complexes. This is achieved by proteolysis mediated by IGFBP proteases, among which the best characterised is human PAPP-A, the first member of the pappalysin family of metzincins. We have previously identified and studied the only archaeal homologue found to date, Methanosarcina acetivorans ulilysin. This is a proteolytically functional enzyme encompassing a pappalysin catalytic domain and a pro-domain involved in maintenance of latency of the zymogen, proulilysin. Once activated, the protein hydrolyses IGFBP-2 to -6 and insulin chain β in vitro. We report here that ulilysin is also active against several other substrates, viz (azo)casein, azoalbumin, and extracellular matrix components. Ulilysin has gelatinolytic but not collagenolytic activity. Moreover, the proteolysis-resistant skeletal proteins actin and elastin are also cleaved, as is fibrinogen, but not plasmin and α1-antitrypsin from the blood coagulation cascade. Ulilysin develops optimal activity at pH 7.5 and strictly requires peptide bonds preceding an arginine residue, as determined by means of a novel fluorescence resonance energy transfer assay, thus pointing to biotechnological applications as an enzyme complementary to trypsin.

Keywords: adamalysin; ADAMs; astacin; IGF; IGFBP protease; metalloprotease; metzincin; pappalysin

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