Abstract
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.
Highlights
Academic Editor: Kwang-Hyun BaekThe paradox of aerobic life is that higher eukaryotic organisms cannot exist without oxygen, but it is potentially dangerous to their existence
GDF11[48-64]wt was converted to the variant with oxidized methionines by treatment with 3% H2 O2, monitoring the reaction progression by reverse-phase HPLC chromatography (RP-HPLC) and mass spectrometry, using the un-oxidized precursor as control
GDF11[48-64]wt was converted to the variant with oxidized methionines by treatment with 3% H2O2, monitoring the reaction progression by reverse-phase HPLC chromatography (RP-HPLC) and mass spectrometry, using the un-oxidized precursor as control
Summary
Academic Editor: Kwang-Hyun BaekThe paradox of aerobic life is that higher eukaryotic organisms cannot exist without oxygen, but it is potentially dangerous to their existence. It is widely accepted that high ROS levels may have deleterious effects on macromolecules such as proteins and different proteolytic systems that operate in a number of different biochemical mechanisms aimed at tissue detoxification. In this context, recent studies assign to APEH (Acylaminoacyl Peptidase or acylamino-acid-releasing enzyme) a crucial role in these mechanisms, given its ability to process and degrade many protein substrates through both exo- and endopeptidase activity [2,3,4,5,6,7,8]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call