The action of neutrophil serine proteases on elastin and its precursor
| Autor: | Laurent Debelle, Laurent Duca, Günther Jahreis, Anthony Rusciani, Reinhard H.H. Neubert, Michael C. Jung, Christian E.H. Schmelzer, Anthony S. Weiss, Andrea Heinz |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Proteases
Neutrophils Molecular Sequence Data Enzyme-Linked Immunosorbent Assay Cathepsin G Cleavage (embryo) Biochemistry Serine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Aromatic amino acids Humans Amino Acid Sequence Protein Precursors Chromatography High Pressure Liquid 030304 developmental biology chemistry.chemical_classification 0303 health sciences integumentary system Tropoelastin biology General Medicine Molecular biology Elastin Amino acid chemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization 030220 oncology & carcinogenesis biology.protein Leukocyte Elastase |
| Zdroj: | Biochimie. 94:192-202 |
| ISSN: | 0300-9084 |
| DOI: | 10.1016/j.biochi.2011.10.006 |
| Popis: | This study aimed to investigate the degradation of the natural substrates tropoelastin and elastin by the neutrophil-derived serine proteases human leukocyte elastase (HLE), proteinase 3 (PR3) and cathepsin G (CG). Focus was placed on determining their cleavage site specificities using mass spectrometric techniques. Moreover, the release of bioactive peptides from elastin by the three proteases was studied. Tropoelastin was comprehensively degraded by all three proteases, whereas less cleavage occurred in mature cross-linked elastin. An analysis of the cleavage site specificities of the three proteases in tropoelastin and elastin revealed that HLE and PR3 similarly tolerate hydrophobic and/or aliphatic amino acids such as Ala, Gly and Val at P1, which are also preferred by CG. In addition, CG prefers the bulky hydrophobic amino acid Leu and accepts the bulky aromatic amino acids Phe and Tyr. CG shows a strong preference for the charged amino acid Lys at P1 in tropoelastin, whereas Lys was not identified at P1 in CG digests of elastin due to extensive cross-linking at Lys residues in mature elastin. All three serine proteases showed a clear preference for Pro at P2 and P4′. With respect to the liberation of potentially bioactive peptides from elastin, the study revealed that all three serine proteases have a similar ability to release bioactive sequences, with CG producing the highest number of these peptides. In bioactivity studies, potentially bioactive peptides that have not been investigated on their bioactivity to date, were tested. Three new bioactive GxxPG motifs were identified; GVYPG, GFGPG and GVLPG. |
| Databáze: | OpenAIRE |
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