Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme

APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actu...

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Published inInternational journal of molecular sciences Vol. 23; no. 1; p. 443
Main Authors Sandomenico, Annamaria, Gogliettino, Marta, Iaccarino, Emanuela, Fusco, Carmela, Caporale, Andrea, Ruvo, Menotti, Palmieri, Gianna, Cocca, Ennio
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 31.12.2021
MDPI
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Summary:APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48-64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity.
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These authors contributed equally to this work.
Present address: Institute of Crystallography, National Research Council (CNR-IC), 34149 Basovizza, Italy.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23010443