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
Subjects
Amino acids
APEH
Chromatography
Endopeptidases
endoproteolytic activity
Enzymatic activity
Enzyme activity
Enzymes
Humans
Methionine
Models, Molecular
Oligopeptidase
Oxidation
Oxidation-Reduction
Oxidative stress
oxidized methionine
oxidized substrates
Peptide Hydrolases - metabolism
Peptides
Peptides - metabolism
Physiology
Prolyl oligopeptidase
Proteins
Residues
Serine proteinase
Substrate Specificity
Sulfoxides
oxidized methionine
APEH
endoproteolytic activity
oxidative stress
oxidized substrates
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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