Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease
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Cynthia Tallant
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.
©2007 by Walter de Gruyter Berlin New York
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Artikel in diesem Heft
- Proteinase Inhibitors and Biological Control – An Attractive International Symposia Series
- Two decades of thyroglobulin type-1 domain research
- Cysteine cathepsin non-inhibitory binding partners: modulating intracellular trafficking and function
- Cysteine proteases: destruction ability versus immunomodulation capacity in immune cells
- ‘Species’ of peptidases
- Protease research in the era of systems biology
- Human and mouse homo-oligomeric meprin A metalloendopeptidase: substrate and inhibitor specificities
- Association of cathepsin E with tumor growth arrest through angiogenesis inhibition and enhanced immune responses
- Characterization and comparative 3D modeling of CmPI-II, a novel ‘non-classical’ Kazal-type inhibitor from the marine snail Cenchritis muricatus (Mollusca)
- Cellular localization of MAGI-1 caspase cleavage products and their role in apoptosis
- Differential methylation kinetics of individual target site strands by T4Dam DNA methyltransferase
- Characterisation of zinc-binding domains of peroxisomal RING finger proteins using size exclusion chromatography/inductively coupled plasma-mass spectrometry
- Defining the extended substrate specificity of kallikrein 1-related peptidases
- Latent MMP-9 is bound to TIMP-1 before secretion
- Novel expression of kallikreins, kallikrein-related peptidases and kinin receptors in human pleural mesothelioma
- Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease
- Clinical chemistry reference database for Wistar rats and C57/BL6 mice
